Approximately 5-10% of chronic myeloid leukemia (CML) patients are found to have structural or numerical additional chromosomal abnormality (ACAs) in addition to the characteristic t(9;22)(q34;q11.2) BCR/ABL1 at the time of diagnosis. The prognostic significance of such additional chromosomal abnormalities has been controversial. Translocation t(11;14)(q13;q32) CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neoplasm. Here we report a unique case describing a patient found at diagnosis of chronic phase CML to have both the Philadelphia chromosome as well as t(11;14)-a rare cytogenetic combination. The patient was treated with imatinib with appropriate hematologic response but persistent disease by FISH and RT-PCR. She was switched to dasatinib and eventually achieved cytogenetic remission in both translocations, but still with persistent RT-PCR evidence of BCR-ABL1 fusion. As cyclin D1 is a regulatory subunit of cyclin-dependent kinases CDK4 and CDK6 and is required for the cells to progress through the G1 phase of the cell cycle, overexpression of cyclin D1 will likely promote cells into cell cycle. This may further augment proliferation in addition to upregulated ABL1 kinase activity in the index case. It may also contribute to the resistance to imatinib, as imatinib only targets on BCR-ABL fusion. Therefore, the addition of t(11;14)(q13;q32) may have significant implication in patient management.
Keywords: Chronic myelogenous leukemia; additional cytogenetic abnormality; prognosis; t(11;14)(q13;q32) CCND1-IGH fusion.
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