t(15;17)(q24.1;q21.2)/PML-RARA in blast phase of chronic myelogenous leukemia: A rare form of clonal evolution

Chronic myelogenous leukemia (CML) in blast phase (BP) is frequently accompanied by cytogenetic abnormalities in addition to t(9;22)(q34;q11.2). We describe a 72-year-old woman with a history of CML, treated with imatinib, and in complete remission for 23 months when she developed sudden coagulopathy as a manifestation of BP. Bone marrow (BM) aspiration and biopsy revealed hypercellular BM with numerous promyelocytes with cytochemical analysis of a BM aspirate smear showing strong myelokperoxidase positivity. Auer rods were also identified. Conventional cytogenetic analysis showed 46,XX,der(3)t(3;15)(q21;q15)t(15;17)(q24.1;q21.2),t(9;22)(q34;q11.2),der(15)t(3;15),del(17)(q21)[20]. The presence of BCR-ABL1 and PML-RARA were confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Molecular studies showed no mutations in ABL1, FLT3, NPM1, RAS, KIT, IDH1, IDH2, and JAK2 genes. The patient was treated with all-trans retinoic acid and arsenic trioxide and achieved complete cytogenetic remission with no evidence of PML-RARA detected by FISH and RT-PCR and low level of BCR-ABL1 fusion transcripts detected by RT-PCR. The patient expired as a result of multiorgan system failure 2 months later. Based on our review of the literature, this is the second confirmed case of CML developing t(15;17)(q24.1;q21.2)/PML-RARA at time of BP. Although the BP resembled de novo acute promyelocytic leukemia (APL) morphologically, this patient had a more aggressive clinical course (compared with de novo APL) and died of complications of therapy.