Blast phase of chronic myeloid leukemia presenting as early T-cell precursor acute lymphoblastic leukemia

Abstract Objectives The blasts in most cases of chronic myeloid leukemia blast phase (CML-BP) have a myeloid or precursor-B immunophenotype, with only a small subset having T-cell or natural killer–cell lineage. Patients with CML-BP having early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) are extremely rare. Methods We report the clinicopathologic, immunophenotypic, and molecular genetic features and outcome of 3 patients with CML-BP who had ETP-ALL, with a review of the literature. Results Only patient 1 had a history of chronic myeloid leukemia chronic phase. Fluorescence in situ hybridization revealed BCR::ABL1 rearrangement in cells with round nuclei (blasts) and cells with segmented nuclei (neutrophils) in cases 2 and 3, supporting a diagnosis of CML-BP rather than de novo Ph+ ETP-ALL. The blasts were positive for cytoplasmic CD3, CD7, CD33, and CD117; were negative for CD1a and CD8; and had dim CD5 expression in 2 cases. Next-generation sequencing showed a TET2 mutation in case 1 and BCOR, RUNX1, and STAG2 mutations in case 3. All patients received chemotherapy and tyrosine kinase inhibitors. Patients 2 and 3 died 33 days and 39 days, respectively, after diagnosis. Patient 1 received stem cell transplantation and was alive 14 months after blast phase. Conclusions Patients with CML-BP may have ETP-ALL. These patients usually have an aggressive clinical course, requiring intensive therapy, and may benefit from stem cell transplantation.