BCR/ABL1 GENE EXPRESSION RATE AT 3 MONTHS OF THYROSINKINASE INHIBITORS THERAPY AS A PROGNOSTIC FACTOR OF THERAPY RESPONSE IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Dmytrenko I. V., Minchenko Zh. M., Martina Z. V., Shlyakhtychenko T. Y., Dmytrenko O. O., Dyagil I. S.

MEDICAL GENETICS

Scentific article

Evaluation of the tyrosinekinase inhibitors (TKIs) therapy response in patients with chronic myeloid leukemia (CML) is based on determination of the residual tumor cells rate at the different stages of the therapy. The main indicator of the TKI therapy efficacy is the rate of BCR/ABL1 gene at 12 months of the therapy but determination of the earliest markers of adverse prognosis is actual. The aim of the study was to investigate the prognostic value of BCR/ABL1 gene expression level at 3 months of therapy regarding the probability of achieving an optimal response on the tyrosinekinase inhibitor therapy in patients with chronic myeloid leukemia. The retrospective study of the TKI therapy response in 161 CML patients with chronic phase (89 men (55.3%) and 72 women (44.7%)) was conducted. The median age of patients was 41 years (18-80 years). In the observation group 141 patients received imatinib at a starting dose of 400 mg per day and 20 patients received nilotinib at a dose of 600 mg per day. The duration of patients follow-up on TKI therapy ranged from 12 to 120 months (median 38 months). 83 patients (48.4%)) were treated with hydroxyurea and/or interferon for 1 – 161 months before being assigned to TKI (median 3 months). The BCR/ABL1 gene expression was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with real-time detection after 3, 6, and 12 months of TKI therapy, and every 6 months thereafter. Univariable analysis showed that low-risk Sokal score, nilotinib therapy, shorter duration of treatment prior to TKI prescribing and a deeper response at 3 months of TKI therapy were the prognostic factors of the optimal response at 12 months of therapy. We calculated threshold of BCR/ABL1 at 3 months of TKI therapy (BCR/ABL1 ≤ 8.55%) with favorable prognosis for the effective achievement of the optimal response at 12-month of TKI therapy. The sensitivity of the model was 100%, specificity – 82.2%. Applying of multivariable logistic regression revealed the independent prognostic factors for achieving of the optimal response at 12-month of TKI therapy: the rate of BCR/ABL1 at 3 months of TKI therapies below 8.55% and the low-risk Sokal score. The information ability of this model was 82.0% (p <0.001). It was shown that the rate of the BCR/ABL1 after 3 months of TKI therapy is an early independent potent prognostic marker that allows to identify patients at high risk of poor response on TKI therapy. Early criteria of adverse prognosis will allow to transfer the patient to the most effective therapy for the shortest term and to prevent the clinical manifestations of TKI resistance. Reducing the duration of cell exposure under oncogenic BCR/ABL1 tyrosinekinase will minimize the risk of new mutations appearance and therefore shorten the probability of TKI resistance development.

chronic myeloid leukemia, BCR/ABL1 gene, molecular monitoring, tyrosine kinase inhibitors, prognostic factors.

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«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 223-226 pages, index UDK 575.224:616.155.392-006.44-085-037:615.27

10.29254/2077-4214-2019-3-152-223-226