Imatinib mesylate therapy may cause additional chromosomal instability by a feedback mechanism in chronic myeloid leukemia treatment

Chronic myeloid leukemia is a myeloproliferative disease, characterized by the presence of the Philadelphia chromosome, which results from the reciprocal chromosomal translocation t(9;22)(q34;q11). Tyrosine kinase inhibitors like imatinib mesylate are selective inhibitors of the BCR–ABL tyrosine kinase, produces high rates of major cytogenetic responses in chronic myeloid leukemia cases. After the imatinib mesylate therapy, some chromosomal abnormalities including trisomy 8, monosomy 7 and nullisomy Y had been reported more frequently. The selective inhibition of tyrosine kinase with imatinib mesylate treatment may cause the proliferation of Philadelphia negative type cell clones. The occurrence of different chromosomal abnormalities including trisomy 8, monosomy 7 and nullisomy Y may have been occurred as a result of an additional chromosomal instability in imatinib mesylate therapy in chronic myeloid leukemia patients. A feedback mechanism due to imatinib mesylate therapy may cause the proliferation of a different Ph-negative stem cell clone with or without chromosomal abnormalities. In the imatinib mesylate treated chronic myeloid leukemia cases, a dosage effect of a gene or an imprinting factor may be the reason of the chromosomal abnormalities. Also a duplication of a mutated/rearranged gene may cause the chromosomal abnormalities due to chromosomal instability. So, we need to clarify these mechanisms in alternative pathways, affected in CML progression.