Is the BCR-ABL/GUSB transcript level at diagnosis an early predictive marker for chronic myeloid leukemia patients treated with imatinib?

The development of the first target-specific tyrosine kinase inhibitor (TKI) and its introduction in the clinical practice radically changed chronic myeloid leukemia (CML) treatment. Monitoring therapeutic response to TKIs is a critical step in the management of CML.1 Recently, several follow-up studies upon which the European Leukemia Net 2013 (ELN) recommendations were based, pointed to the importance of early clearance of leukemic cells as demonstrated by molecular methods. Attaining a BCRABLIS transcript level ≤10% three months after initial imatinib mesylate (IM) treatment was found to be associated with a favorable outcome, including longer progression-free (PFS) and overall survival (OS), and higher probability of achieving complete cytogenetic response (CCyR) and major molecular response (MMR).1 Quantification of the BCR-ABL transcript level reflects leukemic burden, and is carried out by quantitative real-time polymerase chain reaction (RQ-PCR). Molecular response is based on the ratio of BCR-ABL transcript levels and a control gene. Results are expressed according to an international scale (IS) assigned to every patient at diagnosis, which is equal to 100% of BCR-ABL/control gene transcripts, regardless of the absolute amount of BCR-ABL transcripts. Thus, the actual leukemic burden of patients at diagnosis is not taken into account.2 An ideal control gene would be expected to be uniformly expressed in different cell types regardless of its proliferative status as well as be unaffected by therapeutic regimens, constant between individuals and expressed at a level similar to BCR-ABL. In fact, this control gene does not exist, and BCR and ABL are the most widely used control genes for quantifying BCR-ABL transcripts, mainly due to historical reasons. However, both BCR and ABL control genes do not show linearity with BCR-ABL transcript levels above 10% contrary to the GUSB gene that is not affected by high-level distortions which allow for better estimations of the BCR-ABL transcript level at diagnosis.3 In this study, the BCR-ABL transcript levels of 31 CML patients under IM treatment were analyzed by RQ-PCR in matinib?