Philadelphia chromosome-negative but BCR::ABL1-positive acute lymphoblastic leukemia: a real-world multicenter cohort study.

Chronic myelogenous leukemia that carries the BCR::ABL1 fusion gene without cytogenetically detectable Philadelphia (Ph) chromosomes is termed masked Ph. However, the prevalence and clinical relevance of masked Ph in acute lymphoblastic leukemia (ALL) remain unclear. Using the Hokkaido Leukemia Net real-world multicenter cohort, we analyzed 160 B-cell ALL patients diagnosed between 2017 and 2024 with available cytogenetic and molecular data. Among 92 BCR::ABL1-positive cases, 19 (20.7%) lacked a cytogenetically visible Ph chromosome and were classified as masked-Ph ALL. Compared with Ph + ALL, masked-Ph patients were older and had lower white blood cell counts and bone marrow blast percentages at diagnosis. Most BCR::ABL1-positive patients received tyrosine kinase inhibitors (TKIs) during induction, resulting in comparable complete remission rates and similar overall survival between masked-Ph and Ph + ALL; both groups showed superior outcomes compared with BCR::ABL1-negative ALL. The number of metaphases analyzed by G-banding was significantly lower in masked-Ph ALL, suggesting underdetection by conventional cytogenetics. One case exhibited an atypical FISH pattern consistent with a cryptic microinsertion. These findings indicate that masked-Ph ALL is relatively common and may be overlooked without molecular testing, underscoring the importance of incorporating RT-PCR and FISH at diagnosis.