Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy
the additional molecular and chromosomal abnormalities (aca) in ph-positive cells usually considered as a genetic marker of chronic myeloid leukemia (cml) progression. 457 patients in different cml phases received tyrosine kinase inhibitors (1 <sup>st </sup>and 2 <sup>nd </sup>generation) were studied. during therapy 50 cases with additional chromosomal abnormalities in ph <sup>+ </sup>clone (22 of them in chronic cml phase) were revealed (median follow-up from cml diagnosis – 117 months, median imatinib therapy – 62 months). 86 % of patients in chronic phase with ph <sup>+</sup>cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without aca (p < 0.005). the treatment results depend on chromosomal abnormalities detected. in patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (ccr) is achieved only in the later therapy stages. in patients with additional translocations ccr also achieved with imatinib or 2 <sup>nd </sup>generation tki. only a third of patients with additional ph-chromosome or bcr/abl amplification achieved complete suppression of ph <sup>+ </sup>clone using 2 <sup>nd </sup>generation tki. the presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17)(q10) are poor prognostic factors of tki treatment failures.