Acquired pericentric inversion of der(9) with BCR and ABL1 codeletion in chronic myeloid leukemia: a rare cytogenetic...

Chronic myeloid leukemia (CML) is defined by the presence of the BCR::ABL1 fusion gene resulting from the t(9;22)(q34;q11.2) translocation. In addition to this primary rearrangement, secondary chromosomal abnormalities involving chromosomes 9 and 22 may arise during clonal evolution and influence disease progression and response to therapy. Pericentric inversion of chromosome 9 is usually regarded as a constitutional variant. However, when acquired in CML, particularly involving the derivative chromosome 9, it represents a rare secondary abnormality whose biological and clinical significance remains poorly defined.

We report the case of a 37 year old woman diagnosed with chronic phase CML following investigation of marked hyperleukocytosis. Fluorescence in situ hybridization (FISH) confirmed the presence of the BCR::ABL1 fusion in more than 90% of analyzed cells. Metaphase FISH showed the BCR::ABL1 fusion signal on the Philadelphia chromosome and revealed absence of BCR and ABL1 signals on the derivative chromosome 9. Multicolor FISH identified an acquired pericentric inversion involving the derivative chromosome 9, associated with codeletion of BCR and ABL1 sequences. The patient was initially treated with imatinib at a dose of 400 mg per day but failed to achieve complete cytogenetic remission after 24 months, prompting a switch to the second-generation tyrosine kinase inhibitor dasatinib, with a favorable clinical and cytogenetic response.

This case highlights a rare cytogenetic abnormality in CML characterized by acquired pericentric inversion of the derivative chromosome 9 associated with BCR and ABL1 codeletion. Such complex rearrangements likely reflect clonal evolution and may be associated with suboptimal response to first line imatinib therapy. Accurate discrimination between constitutional and acquired inv(9), together with detailed assessment of derivative chromosome 9 integrity, is essential for prognostic stratification. Comprehensive cytogenetic and molecular analyses remain critical for identifying uncommon secondary abnormalities that may influence therapeutic response and clinical outcome in CML.