Integrative Genomic Characterization of Pediatric Acute Myeloid Leukemia Harboring Myb::gata1 Fusion: a Rare Case Report
Year: 2026
Type: article
Study design: Case Report
Abstract: Introduction Pediatric acute myeloid leukemia (pAML) is a biologically heterogeneous malignancy characterized by recurrent genetic alterations that influence prognosis and therapeutic decision-making. The MYB::GATA1 fusion, resulting from the rare t(X;6)(p11;q23) translocation, is primarily associated with infant acute basophilic leukemia and remains poorly characterized due to its rarity. Objective Characterize the clinical and genomic features of a pAML case harboring MYB::GATA1 and explore its potential prognostic implications through integrative genomic analysis. Case Study/Experience We report the case of a female infant diagnosed with pAML presenting with 70.9% leukemic blasts at diagnosis by multiparametric flow cytometry (MFC). Immunophenotypic analysis revealed blasts expressing CD7, CD13, CD33, CD38, CD45, CD117, CD123, and weak cytoplasmic CD41/CD61, with absent expression of CD34, HLA-DR, and MPO, consistent with an immature myeloid phenotype showing partial megakaryocytic differentiation. Molecular screening for recurrent pAML associated alterations, including RUNX1::RUNX1T1, PML::RARA, CBFB::MYH11, BCR::ABL1, KMT2A rearrangements, FLT3-ITD, FLT3-TKD, NPM1, and CEBPA mutations, was negative. Given the absence of clinically relevant molecular findings, comprehensive transcriptomic profiling by RNA sequencing (RNA-Seq) was subsequently performed, identifying the rare MYB::GATA1 fusion as the putative founder genetic event. Conventional cytogenetic analysis revealed a complex karyotype, 48,XX,+8,add(17)(p13),?dup(18)(q21q22),+21[12]/46,XX[8], without evidence of the canonical t(X;6)(p11;q23). These findings suggest a cryptic or complex rearrangement undetectable by conventional cytogenetics and underscore the added value of high-resolution molecular approaches. The patient was treated according to the GELMAI protocol and achieved an excellent response. Sequential MFC monitoring demonstrated a marked reduction in leukemic burden, with measurable residual disease (MRD) levels of 70.9%, < 0.1%, and < 0.1%, with no detectable abnormal myeloid blast population. During treatment, she experienced infectious complications related to the central venous access device, requiring antimicrobial management. No central nervous system involvement, relapse, hematopoietic stem cell transplantation, or death was observed. At the last follow-up in September 2025, the patient remained in complete remission with an ongoing overall survival of approximately 23 months. Discussion and Conclusion This case highlights the utility of integrated immunophenotypic and genomic profiling for the diagnosis of rare pAML subtypes. The detection of MYB::GATA1 exclusively by RNA-Seq underscores the importance of transcriptomic approaches for identifying cryptic genomic alterations. In contrast to historical associations with male sex and basophilic lineages, this case of a female infant with megakaryoblastic differentiation (M7) aligns with recent pioneering descriptions of MYB::GATA1 in M0/M7 subtypes (Hoffmeister et al., 2024). Crucially, while previous reports documented unfavorable outcomes and early relapse within this infant cohort, this patient achieved rapid MRD clearance and sustained remission, providing pivotal evidence of favorable survival.
Institution: Universidade de Brasília
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223158337