Early Predictors of Suboptimal Response to CML Therapy Could Help in Determining Treatment Strategy

Abstract

Chronic myeloid leukemia (CML) respond dramatically to molecular target therapy; imatinib (IM), a first generation tyrosine kinase inhibitor (TKIs). Quantitation of cytokines like Interleukin-6, Interleukin-7 and Transforming growth factor-α plasma levels before IM therapy, could assess early molecular response (EMR) to IM and predict imatinib failure. A case-control study of 30 CML patients and 30 controls. Levels of IL-6, IL-7 and TGF-α were assayed by ELISA (R&D systems, USA) for both controls and patients. The patients' BCR-ABL1 transcript was assayed by real time-quantitative polymerase chain reaction, using ipsogen® BCR-ABL1 Mbcr Kit on the Rotor-Gene Q MDx (Qiagen, USA). Cytokines and BCR-ABL1 levels were done both before therapy and at 3 months follow up.Three months following IM therapy, the patients were divided into improved (n= 27) and non-improved (n= 3) groups; based on the establishment of EMR. Plasma levels of IL-7, IL-6 and TGF-α were significantly higher in CML patients (p< 0.05). Cytokines plasma levels dropped significantly after IM therapy (p< 0.05). Correlation studies revealed a strong positive correlation between pretreatment levels of both IL-6 and TGF-α and posttreatment levels of BCR-ABL transcript (r= 0.89 and 0.84, respectively). IL-7 showed a poor correlation with posttreatment levels of BCR-ABL transcript (r= 0.32). Our study revealed a possible role of IL-6, IL-7 and TGF-α as mediators of CML. The initial high levels of IL-6 and TGF-α was associated with the failure of achieving EMR. The initial high levels of IL-7 in CML patients appears to facilitate the disease process.