BCR::ABL1 e1a2 (p190)-Positive Myeloid Blast Neoplasm: Diagnostic Challenges in Distinguishing De Novo Acute Myeloid Leukemia From Previously Unrecognized Chronic Myeloid Leukemia in the Blast Phase.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene (abelson breakpoint clustering region 1), usually resulting from the reciprocal translocation t(9;22)(q34;q11.2), which generates the Philadelphia chromosome. Most patients with CML express the p210 BCR::ABL1 protein, typically generated by the e13a2 or e14a2 transcripts. In contrast, the e1a2 transcript, which encodes the p190 BCR::ABL1 isoform, is uncommon in CML and is more frequently associated with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. Patients with p190-positive CML often present with atypical clinical features, late diagnosis, rapid progression, and reduced survival. According to the WHO classification, the disease progresses through two phases: a chronic phase and a blast phase. The blast phase (CML-FB) is the most aggressive stage of CML and is associated with a poor clinical prognosis. We present the case of a 48-year-old woman with a two-year history of chronic anemia of unknown origin who developed a blast myeloid neoplasm expressing BCR::ABL1. Peripheral blood analysis showed a marked myeloid predominance with granulocytic precursors in multiple stages of maturation and 35% circulating blasts. Bone marrow examination revealed 35% myeloid blasts expressing CD34, CD117, and myeloperoxidase, with no evidence of lymphoid differentiation. The markers TdT, PAX-5, CD10, CD14, CD36, CD41, and CD20 were negative. Conventional cytogenetic analysis revealed a normal female karyotype (46,XX), while fluorescence in situ hybridization detected the BCR::ABL1 rearrangement. Standard quantitative reverse transcription polymerase chain reaction, designed to detect common p210 transcripts, was negative, while a qualitative assay identified the rare e1a2 transcript (p190). The patient received induction chemotherapy for acute myeloid leukemia (AML) with a 7+3 regimen (continuous infusion of cytarabine for seven days plus an anthracycline for three days) in combination with dasatinib; following consolidation therapy with the high-dose cytarabine (HiDAC) regimen (cytarabine 5 g/m²), minimal residual disease (MRD) assessment yielded a positive result of 0.65%. Consequently, a second cycle of HiDAC was administered with the aim of achieving MRD negativity, and allogeneic hematopoietic stem cell transplantation will be evaluated as a potential consolidation strategy. This case highlights the diagnostic complexity of BCR::ABL1-positive myeloid blast neoplasms. The presence of the e1a2 transcript alone does not allow differentiation of de novo BCR::ABL1-positive AML from CML in the myeloid blast phase. In this patient, the prolonged clinical history of unexplained anemia, the presence of granulocytic precursors at multiple stages of maturation, and the integrated clinicopathological findings suggested a previously undiagnosed CML presenting in the myeloid blast phase; however, the absence of historical samples and a documented chronic phase prevented definitive reconstruction of the disease course. An accurate diagnosis requires the integration of clinical history, peripheral blood and bone marrow morphology, immunophenotype, cytogenetics, and molecular findings.