Analyse moléculaire des variantes de résistance du transcrit BCR-ABL chez les patients sous inhibiteurs de tyrosine kinase

Abstract

Chronic myeloid leukemia (CML) is a malignant hematological disorder characterized by the presence of the Philadelphia chromosome, resulting from the reciprocal translocation t(9;22). This genetic alteration leads to the formation of the BCR-ABL fusion gene, which encodes a constitutively active tyrosine kinase responsible for the uncontrolled proliferation of hematopoietic cells. The introduction of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of patients with CML by targeting the BCR-ABL oncoprotein. However, the emergence of resistance mechanisms may compromise treatment efficacy, making accurate molecular monitoring essential for patient management. This bibliographic study aims to highlight the importance of molecular analysis of the BCR-ABL transcript in patients treated with TKIs. It presents the general and physiopathological aspects of CML, the characteristics of the BCR-ABL fusion gene, diagnostic approaches, as well as therapeutic strategies and treatment monitoring. Particular attention is given to the quantitative assessment of the BCR-ABL transcript and its clinical relevance. Real-time PCR (qPCR) and digital PCR (dPCR) techniques are also discussed in order to evaluate their role in accurate transcript quantification and molecular follow-up of patients. This study emphasizes the importance of molecular monitoring in evaluating therapeutic response and highlights the value of modern molecular techniques, particularly digital PCR, in detecting and quantifying low levels of residual disease, thereby contributing to improved management of CML patients. Due to the unavailability of laboratory reagents, this work did not include an experimental study and is based exclusively on data from the scientific literature.

Keywords: BCR-ABL, Chronic myeloid leukemia, digital PCR, molecular monitoring, quantification, real-time PCR, tyrosine kinase inhibitors.