Independent PML::RARA–positive acute promyelocytic leukemia arising during BCR::ABL1–positive chronic myeloid leukemia

Acute promyelocytic leukemia (APL) arising during the clinical course of BCR::ABL1-positive chronic myeloid leukemia (CML) is rare and may represent either promyelocytic blast phase or the emergence of an independent Philadelphia chromosome-negative clone. We report an octogenarian man with chronic-phase CML who was intolerant to multiple tyrosine kinase inhibitors and underwent temporary discontinuation of asciminib. During molecular relapse, bone marrow examination revealed 88% abnormal promyelocytes with Auer rods and markedly elevated PML::RARA transcripts, whereas BCR::ABL1 transcript levels were more than 3 logs lower than at CML diagnosis. Conventional cytogenetics demonstrated t(15;17) without t(9;22) as the dominant clone, supporting de novo APL arising independently of the residual CML clone. All-trans retinoic acid plus arsenic trioxide achieved molecular remission of PML::RARA and was followed by an initial marked reduction in BCR::ABL1 transcript levels, which subsequently remained detectable at low levels during continued follow-up. This case highlights the importance of integrated cytogenetic and molecular evaluation to distinguish blast phase from independent leukemogenesis in patients with CML who develop cytopenias.