Lithium ameliorates neural differentiation restoring cell death balance in Cornelia de Lange syndrome 2D and 3D models Chiara Parodi, Antonella Lettieri, Paolo Grazioli, Elisabetta Di Fede, Sara Grassi, Esi Taci, Andrea Toscani, Simona Prioni, Stefano Rebellato, Elisa Adele Colombo, Silvia Rasetti, Alessandro Cutarelli, Milena Mariani, Stefania Corti, Palma Finelli, Alessandro Prinetti, Grazia Fazio, Angelo Selicorni, Luciano Conti, Cristina Gervasini, Valentina Massa Cell Death Discovery, 2026 Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that affects almost any organ, including the central nervous system. It leads to a wide range of neurodevelopmental delays, and there are currently no available clinical treatments. CdLS is caused by pathogenic variants in one of the 7 genes coding for the cohesin complex, a multimeric structure responsible for sister chromatid cohesion, or for cohesin ring-interacting proteins. Additionally, altered regulation of molecular pathways during development, including the canonical WNT pathway, can cause CdLS malformations. In our study, we evaluated the positive effects of using lithium as an activator of the canonical WNT pathway to ameliorate neural CdLS phenotype. We have exploited accurate two-dimensional (2D) and three-dimensional (3D) human central nervous system in vitro models representing disease-related neurobiological phenotypes: induced pluripotent stem cells of human origin (hiPSCs) differentiated into neural precursors, neurons, and brain organoids (BOs). CdLS models demonstrate alterations in proliferation and differentiation capabilities when mimicking HDAC8 haploinsufficiency. Furthermore, RNA-seq analysis of BOs revealed that both neuronal differentiation and the WNT pathway are downregulated when treated with the HDAC8 inhibitor alone. Following lithium treatment, cells show an enhanced ability to differentiate into the neuronal lineage. Additionally, our working hypothesis is that a specific mechanism may exist that, by connecting lipid metabolism, canonical WNT pathway, and cell death, results in typical CdLS neurodevelopmental deficits.
Is creatine kinase a valid aid in early cardiac muscle damage detection during treatment for childhood acute lymphoblastic leukemia? A case report Grazia Fazio, Jari Intra, Orsola Montini, Laura Rachele Bettini, Giacomo Gotti, Alessandra Sala, Silvia Bungaro, Giovanni Cazzaniga, Carmelo Rizzari, Adriana Balduzzi, Marco Casati Frontiers in Oncology, 2026 Creatine kinase (CK) is an enzyme that plays a pivotal role in various physiological processes, including metabolism and muscle function. This enzyme is found in high concentrations in skeletal muscle and the myocardium, with lower levels present in the brain. Increases in CK values have been observed in muscle damage and neuromuscular disorders. The potential for cardiotoxicity resulting from the administration of chemotherapeutic agents has been identified in subjects affected by hematological or solid tumors. In the present work, we describe the case story of a child diagnosed with acute lymphoblastic leukemia who exhibited two episodes of asymptomatic, markedly elevated CK values, identified during chemotherapy treatment. Our aim was to investigate the potential of CK as a biomarker for the early detection of cardiac muscle damage during therapy.
A Gut Feeling: An Exploratory Multi-Omics Study of Gut Microbiome Dysbiosis and Metabolome and Lipidome Alterations in GATA2 Deficiency Samuele Roncareggi, Francesca Fioredda, Katia Girardi, Simone Serrao, Giulia Capitoli, Rebecca Fumagalli, Marta Nobile, Grazia Fazio, Fabiola Guerra, Maria Grazia Valsecchi, Stefano Rebellato, Marika Casillo, Maria Rosaria Fantuz, Giovanni Savarese, Giuseppe Paglia, Eleonora Gambineri, Adriana Cristina Balduzzi, Andrea Biondi, Francesco Saettini International Journal of Molecular Sciences, 2026 GATA2 deficiency predisposes patients to recurrent infections, myelodysplastic neoplasms (MDSs), and malignancies through disrupted hematopoiesis and immune dysfunction. The role of the gut microbiome (GM) in this condition remains poorly defined. In this multicenter study, we analyzed GM composition, metabolomic, and lipidomic profiles in 12 Italian GATA2-deficient patients, comparing non-HSCT and post-HSCT GATA2-deficient individuals with healthy controls. Non-HSCT patients showed a relative enrichment of Proteobacteria-associated Gram-negative taxa, accompanied by increased levels of metabolites and lipids previously associated with inflammatory processes. Post-HSCT patients displayed profiles with a trend toward partial normalization of GM composition and metabolic features. Overall, our findings suggest the presence of microbiome and metabolic patterns in GATA2-deficient patients, which may reflect underlying immune and hematopoietic alterations, although these observations should be interpreted as descriptive and require validation in larger cohorts.
FLT3 AS A NEW THERAPEUTIC TARGET IN PRECLINICAL MODELS OF PEDIATRIC BCP-ALL WITH PAX5 REARRANGEMENT Alessia Curto Haematologica, 2026 Introduction: B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, prognosis remains poor in refractory or relapsed cases. PAX5, a transcription factor essential for B-cell development, is frequently altered in BCP-ALL (PAX5-alt), including rearrangements (PAX5r). These lead to repression of genes typically activated by wild-type PAX5 and the upregulation of genes normally repressed by PAX5. Fms-like tyrosine kinase 3 (FLT3) gene was previously reported among PAX5-repressed genes. We aim to investigate FLT3 expression in pediatric PAX5r BCP-ALL and design an effective molecularly targeted treatment in this molecular ALL subgroup.Methods: RNA-seq was used to identify PAX5 fusion genes. FLT3 expression was assessed in pediatric BCP-ALL patients and PDX samples derived from PAX5r cases (AIEOP-BFM ALL protocols 2000, 2009, 2017) by RNA-seq and confirmed with RT-qPCR. HTP screening platform strategy has been applied to test FLT3 inhibitors. Among them, gilteritinib was selected and tested in monotherapy and combined with chemotherapy on NALL-1 cells (PAX5::ETV6) and n=4 PAX5r samples using Annexin V/7-AAD FACS staining. Phosphoflow analysis was performed to evaluate FLT3 activation in NALL-1 cells. Results: FLT3 expression was profiled in 599 consecutive pediatric BCP-ALL patients at diagnosis enrolled in the AIEOP-BFM ALL 2017 study. PAX5r patients (n=26) showed significantly higher median FLT3 expression compared to the whole cohort of patients, and levels comparable to KMT2Ar, ZNF384r, and high-hyperdiploid ALL cases, all known to have high FLT3 expression profiles. These results were confirmed by RT-qPCR in primary PAX5r samples and PAX5r PDXs. None of 10 PAX5r with the highest FLT3 expression levels resulted positive for the most common FLT3-ITD mutation by RT-PCR. 16 PAX5r PDXs were used to perform a high-throughput screening of six FLT3 inhibitors to assess drug sensitivity. Among these, gilteritinib, demonstrated a promising efficacy and toxicity profile. In vitro experiments with NALL-1 cells and PAX5r PDX blasts (n=4) revealed gilteritinib's potent cytotoxicity at nanomolar concentrations, both as a single agent and in combination with chemotherapy (dexamethasone and asparaginase). Phosphoflow analysis further confirmed the high FLT3 expression and constitutive basal activation as measured by phospho-FLT3 levels in NALL-1 cells. Following gilteritinib treatment, a significant reduction in FLT3 phosphorylation was observed (-57.5%, p<0.05). Conclusions: FLT3 is highly expressed in PAX5r BCP-ALL, as already known in KMT2Ar and ZNF384r ALL cases. Ex vivo treatment with gilteritinib induced apoptosis in leukemic cells, both as single-agent and in combination with chemotherapeutics, demonstrating synergistic (dexamethasone) or additive (asparaginase) effects. Further in vivo studies are needed to confirm its efficacy in this molecular ALL subgroup.
A NOVEL HIGHLY RECURRENT FUSION CIRCRNA FROM THE KMT2A::AFF1 FUSION GENE IMPACTING MITOCHONDRIAL METABOLISM IN B-ALL WITH THE T(4;11)(Q213-Q221;Q233) TRANSLOCATION Clelia Tiziana Storlazzi Haematologica, 2026 Introduction: Fusion circRNAs (f-circRNAs) may be generated by the back-splicing of linear fusion transcripts derived from genomic rearrangements. Recently, f-circRNAs from the KMT2A::AFF1 fusion gene, originated by a balanced t(4;11)(q21.3-q22.1;q23.3), were detected by bioinformatics approaches in the B-cell Acute Lymphoblastic Leukemia (B-ALL) RS4;11 cell line, as well as in patients, though their contribution to leukemia has not yet been studied. In this framework, we identified a novel KMT2A::AFF1 f-circRNA back-splicing junction (BSJ) in B-ALL cell lines, investigated its oncogenic role in vitro, and determined its possible recurrence in B-ALL patients harboring the t(4;11) rearrangement.Methods: KMT2A::AFF1 BSJs were investigated by PCR approaches and Sanger sequencing in RNAse R-treated and untreated samples of SEM, ALL-PO, and RS4;11 B-ALL cell lines with the t(4;11) translocation, as well as in pediatric and adult B-ALL patients, both with and without the t(4;11) translocation. The f-circRNA functional role was explored using total RNA-seq profiling of Dicer substrate small-interfering RNA (DsiRNA) BSJ knockdown cells, combined with cell death assays, confocal laser scanning microscopy (CLSM), Seahorse analysis, and transmission electron microscopy (TEM).Results: RT-PCR/Sanger sequencing revealed a BSJ fusing AFF1 exon 8 to KMT2A exon 2 (AK_8_2), enriched in RNAse R-treated versus untreated samples, in three B-ALL cell lines, all carrying the t(4;11)(q24;q23)/KMT2A::AFF1 translocation. This sequence was also found in 8/10 pediatric and 7/10 adult t(4;11)-positive B-ALL patients, including three paired diagnosis-relapse samples, whereas it was absent in 23 t(4;11)-negative B-ALL samples. Total RNA-seq profiling of AK_8_2 knocked-down SEM cells identified upregulated genes involved in oxidative stress response and apoptosis regulation. Cell death analysis confirmed the pro-apoptotic impact of AK_8_2 silencing. Confocal analyses and Seahorse bioenergetic profiling demonstrated overproduction of reactive oxygen species, increased mitochondrial membrane potential, and enhanced mitochondrial function, accompanied by dysmorphic mitochondria, as observed by TEM, after AK_8_2 knockdown. Conclusions: We identified AK_8_2 as a novel f-circRNA BSJ recurrent in t(4;11)-positive B-ALL patients at both diagnosis and relapse. Our data provide evidence of the functional role of this RNA molecule in apoptosis and mitochondrial metabolism, suggesting its potential involvement in B-ALL leukemogenesis.
GERMLINE AND SOMATIC COHESIN GENES ALTERATIONS IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA Domenico Gaspari Haematologica, 2026 Introduction: Leukemia is a complex disease whose molecular mechanisms of malignant transformation are not fully understood. Cohesins are essential proteins forming a complex with key roles not only in canonical DNA binding and chromosome segregation but also in non-canonical regulation of gene expression in both proliferating and post-mitotic cells. Alterations or mutations in genes encoding cohesin components may impair chromosomal stability and contribute to leukemia pathogenesis. Somatic cohesin mutations have been reported in myeloproliferative disorders, pediatric Acute Myeloblastic Leukemia (AML) and pediatric Acute Lymphoblastic Leukemia (ALL), whereas germline mutations cause Cohesinopathies such as the Cornelia de Lange Spectrum (CdLSp). Although cancer prevalence in CdLSp remains uncertain, recent studies suggest a potential predisposition to leukemia and brain tumors. Our previous report of a patient affected by both CdLSp and ALL indicated a possible involvement of germline cohesin mutations in ALL pathogenesis.Methods: We performed Next-Generation Sequencing (NGS) RNA-Seq transcriptomic analysis of 711 consecutive diagnostic and 138 relapse samples of pediatric B/T-ALL (AIEOP-BFM protocol, Italian centers). A custom computational pipeline was developed, including DRAGENTM, fusion detection tools, B-ALL subtype classification, and Differential Expression Analysis. Additional data from both pediatric and adult ALL cohorts were integrated through an international collaboration. Fusion transcripts and germline variants were validated using real-time qPCR. Results: Targeted NGS screening of 120 consecutive pediatric ALL cases identified 11 germline cohesin mutations: 6 missense, 4 in 3′ or 5′ UTRs, and a splice-acceptor variant. RNA sequencing of engineered LCLs revealed 619 differentially expressed genes compared to controls, many involved in key intracellular pathways, suggesting functional disruption due to mutation. Cancer prevalence was also assessed in CdLSp patients, and cohesin variants were analyzed in ALL and pediatric brain tumors. Although no significant increase in cancer incidence was confirmed, low-pathogenic germline cohesin variants might still contribute to tumorigenesis. The computational pipeline for RNA-Seq identified fusion transcripts in 6 B-ALL cases (0.7%), involving STAG1 (n=1), STAG2 (n=4), and NIPBL (n=1). Further analyses of international datasets revealed 9 additional fusions (STAG2 n=6, NIPBL n=3). Whole Genome Sequencing is in progress.Conclusions: Our results clarify the contribution of germline and somatic cohesin alterations to pediatric ALL and highlight their non-canonical roles, supporting the identification of a novel rare molecular subgroup of leukemia within the pediatric population.
PEDIATRIC PAX5-REARRANGED ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IS A HIGH-RISK MOLECULAR SUBGROUP OF B-ALL WITH A POOR MRD-DEPENDENT PROGNOSTIC PROFILE N. Peccatori, A. Curto, D. Silvestri, S. Rebellato, Ž. Antić, et al. Haematologica, 2026 Introduction. PAX5-altered acute lymphoblastic leukemia (PAX5-alt ALL) is a recently defined molecular subtype of BCP-ALL, which displays a specific gene expression and is frequently associated with PAX5 aberrations, including rearrangements (PAX5r). Poor/intermediate outcomes were reported for PAX5-alt ALL. However, evidence on clinical features and prognosis of pediatric PAX5r ALL remains limited.Methods: Clinical data of all newly diagnosed PAX5r ALL patients (pts) (<18 years) enrolled in the consecutive AIEOP-BFM ALL trials (ALL 2000, NCT0061345; ALL 2009, NCT01117441; ALL 2017, NCT03643276) or observational studies in Italy (AIEOP), Germany and Austria (BFM) between 2001-2024, were retrospectively collected. PAX5 gene fusions were identified either by cytogenetics, FISH, targeted-RNAseq or whole-RNA-seq (WTS).Results. Overall, 165 pts with a confirmed PAX5r ALL were included in the study. Sixty-five different fusion gene partners were identified, with JAK2 (n=22), NOL4L (N=18), AUTS2 (n=13) and ETV6 (n=12) as the most frequent ones. Median age was 3.4 yrs (0.4-17.8) and 66.1% of the pts were males. Low incidence of CNS involvement (CNS3, 3.8%) and a high rate of hyperleukocytosis (WBC>100x109/L) (22%) was found. According to NCI criteria, 53.3% had high-risk (HR) status. IKZF1plus profile was found in 15.1% of the pts. A tendency to slow treatment response was observed: 13% of pts had prednisone poor response (PPR), 74.7% were PCR-MRD+ at the end of induction (EOI), with 28.6% showing MRD≥5x10-4, and 31.5% were still PCR-MRD+ at the end of consolidation. Per protocol final risk stratification: 25.8%, 42.9% and 31.3% of the pts were standard-risk (SR), medium-risk (MR) and HR, respectively. Further, we restricted the analyses solely to the consecutive PAX5r pts (n=99) enrolled in the AIEOP-BFM ALL 2017 study and compared their clinical features with all non-PAX5r pts (n=1945) enrolled in the same protocol. ETV6::RUNX1 pts were excluded from the analysis. Lower median age at diagnosis (3.4 vs 4.7 yrs), higher hyperleukocytosis rate (23.2% vs 8%, p<0.001), increased rate of IKZF1plus profile (14.4% vs 7.8%, p=0.02) and NCI HR status (57.6% vs 39.1%, p<0.001) were observed in the PAX5r group. No relevant differences in terms of treatment response and risk-stratification distribution were found between the two groups, except for a higher frequency of PPR (14.4% vs 5.7%, p=0.001) in the PAX5r ALL.With a median follow-up of 3.6 yrs, 5-yr EFS and OS for the AIEOP-BFM ALL 2009/2017 PAX5r pts (n=116) were 66.8±5.0% and 95.3±2.1%, respectively; 5-yr EFS were 100%, 59.8±9.3% and 43.8±12.7% for standard-risk (SR), medium-risk (MR) and high-risk (HR) groups, respectively, indicating that the poor prognostic impact of PAX5r applies only when EOI MRD is positive (MR/HR).Conclusions. This multinational retrospective study indicates that PAX5r ALL is frequently associated with HR clinical features and unfavorable outcomes in non-SR pts.
Philadelphia chromosome-positive acute lymphoblastic leukaemia in children and adolescents: A changing treatment landscape and a methodological challenge Adriana Balduzzi, Maria Grazia Valsecchi, Thai Hoa Tran, Jan Zuna, Veronica Leoni, Gunnar Cario, Grazia Fazio, Virginie Gandemer, Sarah K. Tasian, Inge M. van der Sluis, Nicolò Peccatori, Rosanna Parasole, Stefania Monterisi, Mignon L. Loh, Meenakshi Devidas, Stephen P. Hunger, John A. Kairalla, Paola De Lorenzo, Lewis B. Silverman, Andrea Biondi British Journal of Haematology, 2026 Approximately 3%–5% of paediatric acute lymphoblastic leukaemia (ALL) is driven by the BCR::ABL1 fusion gene resulting from t(9;22)(q34;q11.2), known as Philadelphia chromosome-positive (Ph+) ALL. As the treatment landscape of Ph+ ALL has rapidly shifted in the era of chemoimmunotherapy and tyrosine kinase inhibitors (TKIs), this perspective letter brings together experts to review treatment evolution of paediatric Ph+ ALL over the last two decades, highlight ongoing challenges and delineating future directions in optimizing therapy in successor paediatric Ph+ ALL trials. As shown in large ‘Ponte di Legno’ intergroup retrospective studies, before TKIs, the 7-year event-free survival (EFS) and overall survival (OS) of Ph+ ALL children were ~30% and ~40%, respectively, with intensive multi-agent chemotherapy and haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) offered to all patients with a suitable donor (see references in Supplementary Material).1 An addition of TKIs in subsequent trials led to rapid disease clearance and significant long-term survival improvement. Multiple studies conducted during the past two decades by the European intergroup study on Ph+ ALL (EsPhALL) and/or the Children's Oncology Group (COG) demonstrated significant improvements with 5-year EFS and OS of approximately 60% and 80%, respectively, with continuous TKI-based chemotherapy regimens (Table 1, see references in Supplementary Material).2-6 Importantly, similar EFS and OS rates were observed across trials, regardless of TKI generation (imatinib or dasatinib) and chemotherapy backbone. This precision medicine paradigm also reduced treatment-related toxicity, via omission of prophylactic cranial irradiation for nearly all patients and substantial decrease of HSCT use in CR1. Overall, modern TKI-based therapies have transformed paediatric Ph+ ALL from the once-least favourable subtype of ALL into a more curable entity. Imatinib 340 mg/m2 Post-induction: 18 IT 5 years: 69% (57%–83%) 5 years: 79% (68%–92%) Dasatinib 60 mg/m2 Post day 15 induction: 18 IT 5 years: 60% (46%–74%) 5 years: 86% (76%–96%) Imatinib 300 mg/m2 Post IB: 17 IT + 3 if CNS3 5 years: 57% (49%–65%) 5 years: 72% (64%–79%) Dasatinib 60 mg/m2 Post day 15 IA: 17 IT 5 years: 55% (45%–64%) 5 years: 82% (73%–88%) Modified Total XV-XVI Modified Total XV-XVI Dasatinib 80 mg/m2 Since diagnosis: 19 IT 4 years: 71%a (56%–90%) 4 years: 88%a (81%–96%) Imatinib 300 mg/m2 Since diagnosis: 19 IT 4 years: 49%a (32%–75%) 4 years: 69%a (56%–86%) HSCT in CR1 for children with Ph+ ALL has diminished over the last 20 years from approximately 80% in the EsPhALL2004 trial7 to <10% of patients in the most recent trials (reserved to patients with poor minimal residual disease (MRD) response after 10-week therapy, irrespective of ‘high-risk’ genetics such as IKZF1-plus, whose prognostic relevance remains unclear). The OS of paediatric Ph+ ALL also substantially improved from 40% in the pre-TKI era to 80% with TKI-containing regimens, highlighting post-relapse salvageability in the TKI era. Most patients with relapsed Ph+ ALL can now achieve the second complete remission (CR2) or beyond and proceed to HSCT consolidation (about 30% undergo HSCT in CR2); moreover, the high salvage rates reported in trials do not fully reflect the remarkable recent successes of modern B-cell antigen-targeted immunotherapies, such as blinatumomab, inotuzumab or chimeric antigen receptor T-cell therapies8 (see references in Supplementary Material) which may ultimately improve OS rates further and/or reduce morbidity in post-relapse therapy. Indeed, the incorporation of blinatumomab plus TKI with minimal chemotherapy represents a major paradigm shift in the front-line treatment of adult Ph+ ALL, prompting investigation of analogous strategies in paediatrics. The newly opened international AALL2131/EsPhALL2022 (NCT 06124157, EU CT number 2025-520982-39-00) pilot study with continuous TKI replaces the traditional 8-week consolidation chemotherapy phase with two cycles of blinatumomab and intercalates a third blinatumomab block between subsequent chemotherapy courses (Supplementary Material). This pilot trial aims to establish new baseline outcomes of paediatric Ph+ ALL and to guide future therapeutic options. Use of single-agent TKI ‘maintenance’ therapy in Ph+ ALL patients varies widely across the age spectrum. Most paediatric oncologists stop TKI at 2 years with completion of chemotherapy, although recent identification of the chronic myeloid leukaemia (CML)-like subtype raises the potential for prolonged TKI monotherapy maintenance, similar to approaches used in patients with chronic phase CML. Some paediatric oncologists also use TKI monotherapy after HSCT, for 1 or 2 years as clinically tolerated, although data regarding the potential of this approach in preventing relapse remain limited. In the adult setting, TKI discontinuation has not been standard clinical practice, although very recent data support the feasibility of stopping TKI in patients who did not undergo HSCT (see references in Supplementary Material).9 MRD in Ph+ ALL patients can be monitored using several techniques, including quantitative polymerase chain reaction (qPCR) assessment of BCR::ABL1 fusion (at the transcript or DNA level), qPCR or, more recently, next-generation sequencing (NGS) analysis of immunoglobulin/T-cell receptor (IG/TR) rearrangements or flow cytometry (FC) immunophenotyping. In this context, detectable levels of MRD by any of these techniques may be interpreted by clinicians as signals of disease persistence or recurrence and thereby direct therapeutic interventions. Disease monitoring based on BCR::ABL1 transcript levels is particularly controversial due to its high variability and unclear prognostic significance in paediatric Ph+ ALL. In some cases, BCR::ABL1 qPCR may be frankly positive with concurrent negativity or very low positivity by other methods, consistent with a diagnosis of Ph+ ALL with multilineage involvement (or CML-like ALL) that has been identified in up to one-third of paediatric cases.10 At the current time, it remains challenging to discriminate between primary Ph+ ALL versus CML in lymphoid blast crisis, particularly when the BCR::ABL1 fusion gene encodes for the 210-kD protein (p210). In these cases, physicians may decide to protract TKI treatment because of persistent BCR::ABL1 positivity, similar to the adult Ph+ ALL approach, although growth hindrance remains a relevant concern in paediatric patients. Some experts recommend the monitoring of BCR::ABL1 levels in peripheral blood every 3–6 months post-therapy to detect the early signs of molecular relapse and guide therapeutic decisions.11 However, BCR::ABL1 re-emergence in the absence of overt disease by other MRD assays can be a conundrum for treating physicians, who may opt for a watch-and-wait approach versus initiating TKI monotherapy or multidrug salvage therapy, despite such molecular findings not meeting traditional morphological or newer extended definitions of relapse.12 Similar scenarios may exist when (possibly low) positivity of IG/TR PCR or FC MRD is redetected, suggesting impending relapse (representative case example in Table 2). Notably, children with Ph+ ALL treated with front-line imatinib are more likely to receive dasatinib with second-line salvage chemotherapy upon relapse, even without evidence of emergence of resistance mutations. Newer TKIs (e.g. bosutinib, ponatinib, asciminib, olverembatinib) have also achieved high success in adults with relapsed/refractory Ph+ ALL and are under clinical investigation in children via early phase clinical trials (see references in Supplementary Material).13 Relapse patterns have also changed in the TKI era, with the majority of relapses now occurring after chemotherapy completion compared to ~30% at ≥30 months from diagnosis in the pre-TKI era.2 Indeed, we are aware of three children with Ph+ ALL who relapsed more than 9 years from initial diagnosis (Biondi, Zuna and Loh, personal communication), including one with CML-like disease. Whether prolonged TKI monotherapy would have altered this relapse risk remains unknown. An international ‘Ponte di Legno’ initiative has accordingly been launched to collect real-world data on TKI use after completion of conventional chemotherapy in paediatric Ph+ ALL and to evaluate efficacy of salvage therapies following ‘relapse’ by either standard criteria or by low-level emergence/persistence of MRD. To optimally assess clinical outcomes, details regarding subsequent treatment interventions and prolonged follow-up are needed, which is challenging due to disease rarity and operational burden. Most clinical trials do not routinely capture data after front-line therapy and post-HSCT, partly due to patients being referred to adult institutions for continued care. Robust collection of long-term outcomes may ultimately require a formal registry rather than clinical trials. A more ambitious approach, aimed at optimizing therapeutic plans, calls for adaptive trial designs as in the Sequential, Multiple Assignment, Randomized Trials (SMART),14 which adopt a structured sequence of diagnostic/therapeutic strategies enabling, for instance, the incorporation of innovative treatments for first/impending relapse. The ICH E9(R1) guidelines (see references in Supplementary Material) provide a framework for statistical analysis in the presence of intercurrent events, defined as ‘events occurring after treatment initiation that affect either the interpretation or the existence of the measurements associated with the clinical question of interest’. While the primary estimand (end-point) in Ph+ ALL studies is usually EFS, measured as the time from diagnosis to resistance, relapse, second malignancy or death (whichever occurs first), in future study designs this could incorporate intercurrent events based on additional MRD evaluations during follow-up. This approach could produce a more granular EFS definition, enriching this composite variable with another mode of failure, such as ‘impending relapse’, based on clear time-point(s), cut-offs and MRD assay. For example, the patient described in Table 2 would be considered alive in CR by standard EFS, whereas counted as having an event under this alternative approach. To ensure comparability of results with previous trials, the standard EFS could be added as a sensitivity analysis to the ‘enriched’ EFS. Furthermore, the competing risk approach could be used to estimate the contribution of each EFS component, thus shedding light on the impact of each cause of failure. In conclusion, successful TKI-based therapies during the past two decades have transformed clinical outcomes of children with Ph+ ALL and established a new precedent for precision medicine approaches for other high-risk subtypes of childhood ALL. Recent additional advances in treatment of adult Ph+ ALL (see references in Supplementary Material), particularly intercalation of blinatumomab immunotherapy, reduction of toxic chemotherapy and credentialing of next-generation TKIs,15 challenge paediatric haematologists to investigate similar strategies in children and adolescents. A first step in this direction is the ongoing AALL2131/EsPhALL2022 international study. Efforts should also be made to collect robust information regarding long-term outcomes both from clinical trials and real-world data and to adopt novel statistical approaches to study design and analysis, with the overarching goal of further reducing relapse risk and improving long-term survival with less toxicity. ABa, MGV, ABi, LBS, THT, SKT, SPH, VG and PDL designed the study and wrote the manuscript; all authors reviewed and approved the final manuscript. We thank Valentino Conter for his inspiration and supervision of this paper. We thank Federica Colnaghi for the PCR quantification of BCR::ABL1 transcript of the representative case example. This article was supported by the Italian Ministry of Health within the ‘Ricerca Corrente’ Program. This article was supported by the Italian Ministry of Health within the ‘Ricerca Corrente’ Program. JZ was supported by the Czech Health Research Council NW25-03-00276. JAK and COG operations and Statistics & Data Center are supported by the National Cancer Institute of the National Institutes of Health (U10CA180886, U10CA180899). VG was supported by the Projet Hospitalier de Recherche Clinique-Cancer. GC and the EsPhALL activities in Germany are supported by Deutsche Krebshilfe (#70112958). SKT was supported by the United States National Institutes of Health/National Cancer Institute awards 1U01CA232486 and 1U01CA243072, a Department of Defense Translational Team Science award and a Pennsylvania Department of Health Commonwealth Universal Research Enhancement (CURE) award. SKT is a Scholar of Blood Cancer United (formerly the Leukemia & Lymphoma Society) and holds the Joshua Kahan Endowed Chair in Pediatric Leukemia Research at the Children's Hospital of Philadelphia. SKT receives research funding from Incyte Corporation and Kura Oncology; serves/d on scientific advisory boards for Aleta Biotherapeutics, Amgen, Ascentage Pharmaceuticals, AstraZeneca, C-Further/LifeArc, Kura Oncology, Novartis Pharmaceuticals and Syndax Pharmaceuticals; and has received travel support from Amgen and Jazz Pharmaceuticals (all for unrelated studies). SPH owns common stock in Amgen and has received honoraria from Jazz and Servier. RP has participated in advisory board meetings for Amgen, Novartis, Clinigen and Jazz Pharma and has received honoraria from Amgen for the speaker bureau. GC (or the institution) has received research support or honoraria or travel support from Amgen, Clinigen and Jazz Pharma. The other authors have no conflict of interest. The study was performed according to the Declaration of Helsinki. This manuscript does not report identifiable patient information. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Bone Marrow CD8 + Abundance Inversely Correlates with Progressive Marrow Fibrosis and Myelodysplastic Evolution in GATA2 Deficiency: Case Report Francesca Vendemini, Samuele Roncareggi, Vincenzo L’Imperio, Fabiola Guerra, Federica Mottadelli, Marco Chiarini, Oscar Maglia, Simona Sala, Grazia Fazio, Rocco Piazza, Sonia Bonanomi, Andrea Biondi, Francesco Saettini Journal of Clinical Immunology, 2025 PURPOSE: GATA2 deficiency, a rare inborn error of immunity, presents with highly variable phenotypes. Bone marrow (BM) changes such as hypocellularity and myelodysplastic syndrome (MDS) are common, with hematopoietic stem cell transplantation being the only curative option due to the risk of progression to acute myeloid leukemia. Although traditional markers like cytogenetic abnormalities and somatic mutations (e.g., ASXL1) identify the risk of leukemic transformation, efforts to identify novel predictors of disease evolution are needed. CD8+ T cells are known to play a key role in MDS immune surveillance, but their specific involvement in GATA2 deficiency remains poorly defined. METHODS: In this case report, we report on a young adult with GATA2 deficiency who underwent longitudinal monitoring of both peripheral and BM lymphocyte subsets, with a focus on CD8+ T-cell evolution in relation to MDS progression. RESULTS: The patient exhibited typical GATA2-deficient immune-hematological findings, including monocytopenia, B- and NK-cell deficiency, but had no history of severe infections and remained transfusion-independent. While peripheral CD8+ T-cell levels remained stable over time, a notable reduction in BM CD8+ T cells was observed in association with MDS progression. CONCLUSION: Providing a long-term follow-up of one GATA2-deficient patient, we suggest that a decrease in BM CD8+ T cells may serve as an early marker of immune surveillance escape and disease progression. These findings underscore the need for further investigation into the role of BM CD8+ T cells in GATA2 deficiency and MDS evolution, potentially offering new insights for follow-up and therapeutic intervention.
p300 inhibition delays premature cellular senescence Elisabetta Di Fede, Esi Taci, Silvia Castiglioni, Stefano Rebellato, Silvia Ancona, Paolo Grazioli, Chiara Parodi, Elisa Adele Colombo, Clara Bernardelli, Elena Lesma, Ian Daniel Krantz, Stefania Corti, Alberto Priori, Grazia Fazio, Cristina Gervasini, Valentina Massa, Antonella Lettieri Npj Aging, 2025 Cellular senescence represents a permanent state of cell cycle arrest, also observed in neurodegenerative disorders. As p300 has been identified as an epigenetic driver of replicative senescence, we aimed to investigate whether in vitro p300 inhibition could rescue the stress-induced premature senescence (SIPS) phenotype. We exploited 2D and 3D (brain organoids) in vitro models of SIPS using two different stressor agents. In addition, we combined the treatment with a p300 inhibitor and validated p300 role in SIPS by analyzing different senescence markers and the transcriptome in our models. Interestingly, p300 inhibition can counteract the DNA damage and SIPS phenotype, detecting a dysregulation of gene expression and protein translation associated with the senescence program. These findings highlight both the molecular mechanisms underlying senescence and p300 as a possible pharmacological target. Thus, targeting p300 and, by extension, senescent cells could represent a promising therapeutic strategy for age-related diseases such as neurodegenerative disorders.
Biallelic PI4KA Mutations Disrupt B-Cell Metabolism and Cause B-Cell Lymphopenia and Hypogammaglobulinemia Francesco Saettini, Fabiola Guerra, Mario Mauri, Claire G. Salter, Margaret P. Adam, David Adams, Emma L. Baple, Estibaliz Barredo, Sanil Bhatia, Arndt Borkhardt, Alfredo Brusco, Cristina Bugarin, Clizia Chinello, Andrew H. Crosby, Precilla D’Souza, Vanna Denti, Grazia Fazio, Silvia Giuliani, Hye Sun Kuehn, Hassan Amel, Asha Elmi, Bernice Lo, Federica Malighetti, Giorgia Mandrile, Andrea Martín-Nalda, Heather C. Mefford, Daniele Moratto, Fatemeh Emam Mousavi, Zoe Nelson, Luis González Gutiérrez-Solana, Ellen Macnamara, Vincent Michaud, Melanie O’Leary, Lisa Pagani, Lisa Pavinato, Patricia VVelez Santamaria, Laura Planas-Serra, Manuel Quadri, Miquel Raspall-Chaure, Stefano Rebellato, Sergio D. Rosenzweig, Agathe Roubertie, Dirk Holzinger, Christin Deal, Catherine Walsh Vockley, Angela Maria Savino, Jennifer L.Stoddard, Holm H. Uhlig, Aurora Pujol, Fulvio Magni, Giuseppe Paglia, Gianni Cazzaniga, Rocco Piazza, Matteo Barberis, Andrea Biondi Journal of Clinical Immunology, 2025
Impact of ATLG on CD4+ T-cell reconstitution after HSCT in children: a detailed immune profiling study Marco M. Sindoni, Anita Toso, Francesca Limido, Cristina Bugarin, Tiziana Villa, Sarah Bonte, Yvan Saeys, Chiara Buracchi, Giulia Prunotto, Virginia Meda Spaccamela, Mathias Hauri, Oscar Maglia, Simona Sala, Domenico Gaspari, Grazia Fazio, Andrea Biondi, Adriana Balduzzi, Silvia Nucera, Giuseppe Gaipa Cytotherapy, 2025
Cohesins: Crossroad Between Cornelia de Lange Spectrum and Cancer Predisposition Laura Rigotti, Stefano Rebellato, Antonella Lettieri, Silvia Castiglioni, Milena Mariani, Simona Totaro, Claudia Saitta, Cristina Gervasini, Grazia Fazio, Valentina Massa, Giovanni Cazzaniga, Angelo Selicorni American Journal of Medical Genetics Part A, 2025
PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome Aurélie Caye-Eude, Grazia Fazio, Agata Pastorczak, Judith M. Boer, Doris Steinemann, Debdutta Ganguli, Edwin Sonneveld, Sabrina Haslinger, Lucía D’Andrea, Jutta Bradtke, Bruno A. Lopes, Marketa Zaliova, Gabriele Escherich, Margit König, Klaus Fortschegger, Andrea Inthal, Irina Stasevich, Mariana Emerenciano, Jan Trka, Luis Castillo, Mayur Parihar, Anthony V. Moorman, Anke K. Bergmann, Monique L. den Boer, Wojciech Młynarski, Giovanni Cazzaniga, Hélène Cavé, Karin Nebral, Dagmar Schinnerl, Sabine Strehl Leukemia, 2025
Antibody Deficiency in Patients with Biallelic KARS1 Mutations Francesco Saettini, Fabiola Guerra, Grazia Fazio, Cristina Bugarin, Hugh J McMillan, Akira Ohtake, Anna Ardissone, Masayuki Itoh, Sabrina Giglio, Gerarda Cappuccio, Giuliana Giardino, Roberta Romano, Manuel Quadri, Serena Gasperini, Daniele Moratto, Marco Chiarini, Ishiguro Akira, Yasuyuki Fukuhara, Itaru Hayakawa, Yasushi Okazaki, Mario Mauri, Rocco Piazza, Gianni Cazzaniga, Andrea Biondi Journal of Clinical Immunology, 2023
miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease Carolina Caserta, Silvia Nucera, Matteo Barcella, Grazia Fazio, Matteo Maria Naldini, Riccardo Pagani, Francesca Pavesi, Giacomo Desantis, Erika Zonari, Mariella D’Angiò, Paola Capasso, Angelo Lombardo, Ivan Merelli, Orietta Spinelli, Alessandro Rambaldi, Fabio Ciceri, Daniela Silvestri, Maria Grazia Valsecchi, Andrea Biondi, Giovanni Cazzaniga, Bernhard Gentner Leukemia, 2023
The recombinome of IKZF1 deletions in B-cell precursor ALL Bruno A. Lopes, Claus Meyer, Heloysa Bouzada, Marius Külp, Ana Luiza Tardem Maciel, Patrizia Larghero, Thayana C. Barbosa, Caroline P. Poubel, Caroline Barbieri, Nicola C. Venn, Luciano Dalla Pozza, Draga Barbaric, Chiara Palmi, Grazia Fazio, Claudia Saitta, Thais F. Aguiar, Mecneide M. Lins, Maura R. V. Ikoma-Colturato, Marcia Schramm, Eduardo Chapchap, Gianni Cazzaniga, Rosemary Sutton, Rolf Marschalek, Mariana Emerenciano Leukemia, 2023
Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia Chiara Palmi, Silvia Bresolin, Stefanie Junk, Grazia Fazio, Daniela Silvestri, Marketa Zaliova, Athanasios Oikonomou, Katerina Scharov, Martin Stanulla, Anja Moericke, Martin Zimmermann, Martin Schrappe, Barbara Buldini, Sanil Bhatia, Arndt Borkhardt, Claudia Saitta, Marta Galbiati, Michela Bardini, Luca Lo Nigro, Valentino Conter, Maria Grazia Valsecchi, Andrea Biondi, Geertruy te Kronnie, Gunnar Cario, Giovanni Cazzaniga Hemasphere, 2023
The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease Erica Dander, Paola Vinci, Stefania Vetrano, Camilla Recordati, Rocco Piazza, Grazia Fazio, Donatella Bardelli, Mattia Bugatti, Francesca Sozio, Andrea Piontini, Sonia Bonanomi, Luca Bertola, Elena Tassistro, Maria Grazia Valsecchi, Stefano Calza, William Vermi, Andrea Biondi, Annalisa Del Prete, Silvano Sozzani, Giovanna D’Amico Jci Insight, 2023
Circulating cell-free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre-analytical biases Roberta Soscia, Irene Della Starza, Lucia Anna De Novi, Caterina Ilari, Michela Ansuinelli, Marzia Cavalli, Vittorio Bellomarino, Luciana Cafforio, Mariangela Di Trani, Giovanni Cazzaniga, Grazia Fazio, Alessandra Santoro, Domenico Salemi, Orietta Spinelli, Manuela Tosi, Carolina Terragna, Valentina Robustelli, Teresa Bellissimo, Gioia Colafigli, Massimo Breccia, Sabina Chiaretti, Alice Di Rocco, Maurizio Martelli, Anna Guarini, Ilaria Del Giudice, Robin Foà Hematological Oncology, 2023
PAX5 fusion genes are frequent in poor risk childhood acute lymphoblastic leukaemia and can be targeted with BIBF1120 Grazia Fazio, Silvia Bresolin, Daniela Silvestri, Manuel Quadri, Claudia Saitta, Elena Vendramini, Barbara Buldini, Chiara Palmi, Michela Bardini, Andrea Grioni, Silvia Rigamonti, Marta Galbiati, Stefano Mecca, Angela Maria Savino, Alberto Peloso, Jia-Wey Tu, Sanil Bhatia, Arndt Borkhardt, Concetta Micalizzi, Luca Lo Nigro, Franco Locatelli, Valentino Conter, Carmelo Rizzari, Maria Grazia Valsecchi, Geertruij te Kronnie, Andrea Biondi, Giovanni Cazzaniga Ebiomedicine, 2022
Identical EP300 variant leading to Rubinstein–Taybi syndrome with different clinical and immunologic phenotype Francesco Saettini, Grazia Fazio, Maria Teresa Bonati, Daniele Moratto, Valentina Massa, Elisabetta Di Fede, Silvia Castiglioni, Daniela Marchetti, Marco Chiarini, Alessandra Sottini, Maria Iascone, Giovanni Cazzaniga, Luisa Imberti, Andrea Biondi, Cristina Gervasini, Raffaele Badolato American Journal of Medical Genetics Part A, 2022
Recurrent Germline Variant in RAD21 Predisposes Children to Lymphoblastic Leukemia or Lymphoma Anne Schedel, Ulrike Anne Friedrich, Mina N. F. Morcos, Rabea Wagener, Juha Mehtonen, Titus Watrin, Claudia Saitta, Triantafyllia Brozou, Pia Michler, Carolin Walter, Asta Försti, Arka Baksi, Maria Menzel, Peter Horak, Nagarajan Paramasivam, Grazia Fazio, Robert J Autry, Stefan Fröhling, Meinolf Suttorp, Christoph Gertzen, Holger Gohlke, Sanil Bhatia, Karin Wadt, Kjeld Schmiegelow, Martin Dugas, Daniela Richter, Hanno Glimm, Merja Heinäniemi, Rolf Jessberger, Gianni Cazzaniga, Arndt Borkhardt, Julia Hauer, Franziska Auer International Journal of Molecular Sciences, 2022
Validation of the EuroClonality-NGS DNA capture panel as an integrated genomic tool for lymphoproliferative disorders J. Stewart, J. Gazdová, N. Darzentas, D. Wren, P. Proszek, G. Fazio, S. Songia, M. Alcoceba, M. Sarasquete, P. Villarese, M. Y. van der Klift, K. Heezen, N. McCafferty, K. Pal, M. Catherwood, C. Kim, S. Srivastava, L. Kroeze, E. Hodges, K. Stamatopoulos, W. Klapper, E. Genuardi, S. Ferrero, M. van den Brand, G. Cazzaniga, F. Davi, L. Sutton, R. García-Sanz, P. Groenen, E. Macintyre, M. Brüggemann, C. Pott, A. Langerak, D. Gonzalez Blood Advances, 2021
Case Report: Hypomorphic Function and Somatic Reversion in DOCK8 Deficiency in One Patient With Two Novel Variants and Sclerosing Cholangitis Francesco Saettini, Grazia Fazio, Daniele Moratto, Marta Galbiati, Nicola Zucchini, Davide Ippolito, Marco Emilio Dinelli, Luisa Imberti, Mario Mauri, Maria Luisa Melzi, Sonia Bonanomi, Alessio Gerussi, Marinella Pinelli, Chiara Barisani, Cristina Bugarin, Marco Chiarini, Mauro Giacomelli, Rocco Piazza, Giovanni Cazzaniga, Pietro Invernizzi, Silvia Clara Giliani, Raffaele Badolato, Andrea Biondi Frontiers in Immunology, 2021
Recurrent genetic fusions redefine MLL germ line acute lymphoblastic leukemia in infants Grazia Fazio, Michela Bardini, Paola De Lorenzo, Andrea Grioni, Manuel Quadri, Lucia Pedace, Lilia Corral Abascal, Sonia Palamini, Chiara Palmi, Barbara Buldini, Luciana Vinti, Rosanna Parasole, Elena Barisone, Marco Zecca, Claudio Favre, Franco Locatelli, Valentino Conter, Carmelo Rizzari, Maria Grazia Valsecchi, Andrea Biondi, Giovanni Cazzaniga Blood, 2021
Insights into the role of the microbiota and of short-chain fatty acids in rubinstein–taybi syndrome Elisabetta Di Fede, Emerenziana Ottaviano, Paolo Grazioli, Camilla Ceccarani, Antonio Galeone, Chiara Parodi, Elisa Adele Colombo, Giulia Bassanini, Grazia Fazio, Marco Severgnini, Donatella Milani, Elvira Verduci, Thomas Vaccari, Valentina Massa, Elisa Borghi, Cristina Gervasini International Journal of Molecular Sciences, 2021
Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C. Orellana, Grazia Fazio, Fred H. Rodriguez, Loreani P. Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G. M. Kroes, Daniele Moratto, Monique M. van Oostaijen-ten Dam, Frank Baas, Silvère van der Maarel, Rocco Piazza, Zeynep H. Coban-Akdemir, James R. Lupski, Bo Yuan, Ivan K. Chinn, Lucia Daxinger, Andrea Biondi Blood, 2021
Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis Marta Isidro-Hernández, Andrea Mayado, Ana Casado-García, Jorge Martínez-Cano, Chiara Palmi, Grazia Fazio, Alberto Orfao, Jordi Ribera, Josep Maria Ribera, Lurdes Zamora, Javier Raboso-Gallego, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Rafael Jiménez, Francisco Javier García Criado, María Begoña García Cenador, Manuel Ramírez-Orellana, Giovanni Cazzaniga, César Cobaleda, Carolina Vicente-Dueñas, Isidro Sánchez-García Scientific Reports, 2020
Sleeping Beauty–engineered CAR T cells achieve antileukemic activity without severe toxicities Chiara F. Magnani, Giuseppe Gaipa, Federico Lussana, Daniela Belotti, Giuseppe Gritti, Sara Napolitano, Giada Matera, Benedetta Cabiati, Chiara Buracchi, Gianmaria Borleri, Grazia Fazio, Silvia Zaninelli, Sarah Tettamanti, Stefania Cesana, Valentina Colombo, Michele Quaroni, Giovanni Cazzaniga, Attilio Rovelli, Ettore Biagi, Stefania Galimberti, Andrea Calabria, Fabrizio Benedicenti, Eugenio Montini, Silvia Ferrari, Martino Introna, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi Journal of Clinical Investigation, 2020
Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols Gunnar Cario, Veronica Leoni, Valentino Conter, Andishe Attarbaschi, Marketa Zaliova, Lucie Sramkova, Gianni Cazzaniga, Grazia Fazio, Rosemary Sutton, Sarah Elitzur, Shai Izraeli, Melchior Lauten, Franco Locatelli, Giuseppe Basso, Barbara Buldini, Anke K. Bergmann, Jana Lentes, Doris Steinemann, Gudrun Göhring, Brigitte Schlegelberger, Oskar A. Haas, Denis Schewe, Swantje Buchmann, Anja Moericke, Deborah White, Tamas Revesz, Martin Stanulla, Georg Mann, Nicole Bodmer, Nira Arad-Cohen, Jan Zuna, Maria Grazia Valsecchi, Martin Zimmermann, Martin Schrappe, Andrea Biondi Haematologica, 2020
Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects Mara Mazzola, Alex Pezzotta, Grazia Fazio, Alessandra Rigamonti, Erica Bresciani, Germano Gaudenzi, Maria Chiara Pelleri, Claudia Saitta, Luca Ferrari, Matteo Parma, Monica Fumagalli, Andrea Biondi, Giovanni Cazzaniga, Anna Marozzi, Anna Pistocchi Journal of Cellular and Molecular Medicine, 2020
Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions Claus Meyer, Bruno A. Lopes, Aurélie Caye-Eude, Hélène Cavé, Chloé Arfeuille, Wendy Cuccuini, Rosemary Sutton, Nicola C. Venn, Seung Hwan Oh, Grigory Tsaur, Gabriele Escherich, Tobias Feuchtinger, Hansen J. Kosasih, Seong L. Khaw, Paul G. Ekert, Maria S. Pombo-de-Oliveira, Audrey Bidet, Bardya Djahanschiri, Ingo Ebersberger, Marketa Zaliova, Jan Zuna, Zuzana Zermanova, Vesa Juvonen, Renate Panzer Grümayer, Grazia Fazio, Gianni Cazzaniga, Patrizia Larghero, Mariana Emerenciano, Rolf Marschalek Leukemia, 2019
Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study on behalf of the EuroClonality-NGS working group, Monika Brüggemann, Michaela Kotrová, Henrik Knecht, Jack Bartram, Myriam Boudjogrha, Vojtech Bystry, Grazia Fazio, Eva Froňková, Mathieu Giraud, Andrea Grioni, Jeremy Hancock, Dietrich Herrmann, Cristina Jiménez, Adam Krejci, John Moppett, Tomas Reigl, Mikael Salson, Blanca Scheijen, Martin Schwarz, Simona Songia, Michael Svaton, Jacques J. M. van Dongen, Patrick Villarese, Stephanie Wakeman, Gary Wright, Giovanni Cazzaniga, Frédéric Davi, Ramón García-Sanz, David Gonzalez, Patricia J. T. A. Groenen, Michael Hummel, Elizabeth A. Macintyre, Kostas Stamatopoulos, Christiane Pott, Jan Trka, Nikos Darzentas, Anton W. Langerak Leukemia, 2019
Antenatal Microbial Colonization of Mammalian Gut Elisa Borghi, Valentina Massa, Marco Severgnini, Grazia Fazio, Laura Avagliano, Elena Menegola, Gaetano Pietro Bulfamante, Giulia Morace, Francesca Borgo Reproductive Sciences, 2019
NIPBL: A new player in myeloid cell differentiation Mara Mazzola, Gianluca Deflorian, Alex Pezzotta, Laura Ferrari, Grazia Fazio, Erica Bresciani, Claudia Saitta, Luca Ferrari, Monica Fumagalli, Matteo Parma, Federica Marasca, Beatrice Bodega, Paola Riva, Franco Cotelli, Andrea Biondi, Anna Marozzi, Gianni Cazzaniga, Anna Pistocchi Haematologica, 2019
Antileukemic efficacy of BET inhibitor in a preclinical mouse model of MLL-AF4 + infant ALL Michela Bardini, Luca Trentin, Francesca Rizzo, Margherita Vieri, Angela M. Savino, Patricia Garrido Castro, Grazia Fazio, Eddy H.J. Van Roon, Mark Kerstjens, Nicholas Smithers, Rab K. Prinjha, Geertruy Te Kronnie, Giuseppe Basso, Ronald W. Stam, Rob Pieters, Andrea Biondi, Gianni Cazzaniga Molecular Cancer Therapeutics, 2018
Intragenic amplification of PAX5: A novel subgroup in B-cell precursor acute lymphoblastic leukemia? Claire Schwab, Karin Nebral, Lucy Chilton, Cristina Leschi, Esmé Waanders, Judith M. Boer, Markéta Žaliová, Rosemary Sutton, Ingegerd Ivanov Öfverholm, Kentaro Ohki, Yuka Yamashita, Stefanie Groeneveld-Krentz, Eva Froňková, Marleen Bakkus, Joelle Tchinda, Thayana da Conceição Barbosa, Grazia Fazio, Wojciech Mlynarski, Agata Pastorczak, Giovanni Cazzaniga, Maria S. Pombo-de-Oliveira, Jan Trka, Renate Kirschner-Schwabe, Toshihiko Imamura, Gisela Barbany, Martin Stanulla, Andishe Attarbaschi, Renate Panzer-Grümayer, Roland P. Kuiper, Monique L. den Boer, Hélène Cavé, Anthony V. Moorman, Christine J. Harrison, Sabine Strehl Blood Advances, 2017
Williams syndrome and mature B-Leukemia: A random association? Valentina Decimi, Grazia Fazio, Fabiola Dell'Acqua, Silvia Maitz, Marta Galbiati, Carmelo Rizzari, Andrea Biondi, Giovanni Cazzaniga, Angelo Selicorni European Journal of Medical Genetics, 2016
CyclinD1 Down-Regulation and Increased Apoptosis Are Common Features of Cohesinopathies Grazia Fazio, Carles Gaston‐Massuet, Laura Rachele Bettini, Federica Graziola, Valeria Scagliotti, Anna Cereda, Luca Ferrari, Mara Mazzola, Gianni Cazzaniga, Antonio Giordano, Franco Cotelli, Gianfranco Bellipanni, Andrea Biondi, Angelo Selicorni, Anna Pistocchi, Valentina Massa Journal of Cellular Physiology, 2016
