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Chronic Myeloid Leukemia Progressing to Early T-Cell Precursor Lymphoblastic Blast Phase Following Treatment Default: An Integrated Morphologic, Immunophenotypic, Cytogenetic, and Molecular Case Report

Year: 2026

Type: article

Abstract: Chronic myeloid leukemia (CML) is a BCR::ABL1-positive myeloid neoplasm characterized by the Philadelphia chromosome resulting from t(9;22)(q34;q11.2). Although tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in chronic-phase CML, progression to blast phase remains an important feature of advanced disease. The majority of CML blast-phase cases demonstrate myeloid or precursor B-cell differentiation, whereas T-lineage transformation is uncommon. Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) represents an immature T-lineage neoplasm characterized by expression of cytoplasmic CD3 and CD7, weak or absent expression of conventional mature T-cell antigens, and frequent expression of myeloid or stem-cell-associated markers. A 35-year-old man with a known diagnosis of CML in chronic phase, receiving dasatinib and reported to be a frequent treatment defaulter, presented with blast transformation. Peripheral blood examination demonstrated marked leukocytosis, anemia, and thrombocytopenia, with 64% circulating blasts. The blasts were large, with scant cytoplasm and pleomorphic nuclei. Flow cytometric immunophenotyping identified an abnormal blast population comprising approximately 82% of viable events. The blasts expressed CD34, HLA-DR, CD123, cytoplasmic CD3, CD5 (dim), CD7, CD13, and CD33, with variable expression of CD117 and CD56. They were negative for surface CD3, CD1a, CD4, CD8, B-lineage markers, TCR-γδ, and myeloperoxidase. The overall immunophenotype was consistent with ETP-ALL. Cytogenetic analysis demonstrated 47,XY,del(7)(q21),+8,t(9;22)(q34;q11.2), indicating the presence of the Philadelphia chromosome together with trisomy 8 and del(7q). Molecular analysis detected an ABL1 p.Phe317Leu (F317L) kinase-domain mutation. This case represents a rare instance of CML blast phase with an ETP lymphoblastic phenotype and demonstrates the coexistence of an ABL1 F317L kinase-domain mutation and additional cytogenetic abnormalities, including trisomy 8 and del(7q). The case emphasizes the importance of integrating the clinical history with morphologic, flow cytometric, cytogenetic, and molecular findings when an immature T-cell leukemia is identified in a patient with established CML.

Source: Cureus

DOI: 10.7759/cureus.117154