International Journal of Hematology and Oncology 2018, Vol 28, Num 3 Page(s): 154-161
Early Predictors of Suboptimal Response to CML Therapy Could Help in Determining Treatment Strategy

Mohammed M.A. EID1, Marwa M.A. Abd El HAFEEZ1, Hend N. ELLITHY2, Heba M.Z. ELABDIN3, Ghada M. EZZAT1

1Fayoum University, Faculty of Medicine, Department of Clinical Pathology, EGYPT
2Cairo University, Faculty of Medicine, Department of Clinical Hematology, EGYPT
3Fayoum University, Faculty of Medicine, Department of Internal Medicine, Fayoum City, EGYPT

Keywords: Chronic myeloid leukemia, Imatinib, Early molecular response
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.