ABL Kinase Domain Mutations in Iranian Chronic Myeloid Leukemia Patients with Resistance to Tyrosine Kinase Inhibitors.

Abstract

Tyrosine kinase inhibitors (TKIs) are considered standard first-line treatment in patients with chronic myeloid leukemia. Because ABL kinase domain mutations are the most common causes of treatment resistance, their prevalence and assessment during treatment may predict subsequent response to therapy. The molecular response in Bcr-Abl1IS was tested via quantitative real-time polymerase chain reaction. We used the direct sequencing technique to discover the mutations in the ABL kinase domain. The IRIS trial established a standard baseline for measurement - (100% BCR-ABL1 on the 'international scale') and a major molecular response (good response to therapy) was defined as a 3-log reduction in the amount of BCR-ABL1 - 0.1% BCR-ABL1 on the international scale. We observed 11 different mutations in 13 patients, including E255K, which had the highest mutation rate. A lack of hematologic response was found in 22 patients, who showed a significantly higher incidence of mutations. Detection of kinase domain mutations is a reliable method for choosing the best treatment strategy based on patients' conditions, avoiding ineffective treatments, and running high-cost protocols in patients with acquired resistance to TKIs.