KMT2A rearrangement

P=N/A, N=20, Recruiting, University of Freiburg

This case highlights the diagnostic complexity and aggressive clinical course of neonatal MPAL, particularly in the absence of KMT2A rearrangements, and emphasizes the biological heterogeneity of this entity. Strict application of WHO/ICC lineage-defining criteria is essential to ensure accurate classification. Exchange transfusion may serve as a feasible bridging cytoreductive strategy in neonates with life-threatening hyperleukocytosis when leukapheresis is not available, although its effects are temporary and do not replace definitive therapy. Early recognition, prompt supportive management, and improved molecular characterization are critical to optimizing outcomes in this rare and high-risk population.

Patients treated with venetoclax plus intensive chemotherapy (Ven+IC) showed the best composite complete remission (CRc) rate and OS compared to intensive chemotherapy, venetoclax plus reduced-intensive chemotherapy, and reduced-intensive chemotherapy (CRc rate: 89.5% vs. 62.4% vs. 57.3% vs. 61.4%; median OS: not reached vs. 39.9 months vs. 34.8 months vs. 12.7 months). Multivariate analysis identified multiparameter flow cytometry minimal residual disease negativity post-induction therapy, allogeneic hematopoietic stem cell transplantation, and Ven+IC as independent favorable prognostic factors for event-free survival (EFS), and KMT2A::MLLT4 fusion, EVI1 overexpression were independent unfavorable prognostic factors for EFS. In summary, our study showed characteristics and prognostic implications in newly diagnosed KMT2Ar AML in China.

Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

allo-HSCT in CR(1) significantly improves prognosis in these patients. The KMT2A-PTD group showed poor response to conventional intensive chemotherapy but achieved significantly improved prognosis with venetoclax-based therapy.

We confirm miR-93 upregulation in patient samples, suggesting its suitability as a biomarker for CNS involvement. Critically, miR-93 knockdown impairs CNS leukemia engraftment, highlighting its niche-specific role.

P1/2, N=263, Active, not recruiting, Kura Oncology, Inc. | Recruiting --> Active, not recruiting

P1, N=0, Withdrawn, Children's Oncology Group | N=29 --> 0 | Not yet recruiting --> Withdrawn

P1, N=24, Recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Jul 2026 --> Oct 2026

The combination of genetics and MRD allows accurate identification of adult Ph- ALL patients candidates to alloHSCT or chemotherapy. The trial was registered at www.ClinicalTrials.gov: NCT04179929.

P=N/A, N=20, Recruiting, The First Affiliated Hospital of Soochow University

Second, high-resolution molecular profiling should be used to identify high-risk patients and guide pre-emptive or combinatorial interventions based on the molecular underpinnings of CD19- relapse. Together, these approaches will deepen mechanistic insight into CD19- relapse and enable targeted prevention and management of this key limitation of CAR T-cell therapy.