Abstract
Blast phase (BP) transformation in chronic myeloid leukemia (CML) represents a progression to an aggressive clinical state with dismal outcomes. While most cases exhibit myeloid lineage, rare transformations to megakaryoblastic, mixed phenotype, or undifferentiated forms pose significant diagnostic and therapeutic challenges. In this case series we describe the clinicopathological, immunophenotypic, and molecular features of three rare CML-BP cases and emphasize the role of integrated diagnostics in identifying atypical blast phenotypes. Three adult CML patients presenting in BP were evaluated using peripheral smear morphology, bone marrow examination, immunohistochemistry, multiparameter flow cytometry, and molecular analysis for BCR::ABL1 transcript variants. The first case demonstrated megakaryoblastic transformation with CD41/CD61 positivity. The second case presented as acute undifferentiated leukemia, with blasts lacking definitive lineage markers. The third case exhibited a mixed B/monocytic phenotype consistent with MPAL-B/M, confirmed by dual-lineage antigen expression. All cases expressed the p210 BCR::ABL1 transcript, supporting a diagnosis of CMLrelated secondary blast crisis. Outcomes varied, with one patient achieving molecular remission post-transplant, while others experienced treatment-related complications or succumbed to disease. Atypical phenotypes in CML-BP require a high index of suspicion. Timely integration of flowcytometry and molecular diagnostics is critical to distinguish secondary blast transformation from de novo leukemia and to guide appropriate management strategies.