Association between Altered Expression and Genetic Variations of Transforming Growth Factor β-Smad Pathway with Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of and genes. dependent and independent pathways play equally important role in CML. TGFβ-Smad pathway, an important independent pathway, has scarce data in CML. Present study investigate the association between TGFβ-Smad pathway and CML. Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM). serum levels were evaluated by ELISA and transcript levels of receptors, and were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0. serum levels were significantly elevated ( = 0.02) and and were significantly down-regulated ( = 0.012 and = 0.043 respectively) in the patients. c.69A>G in , c.1024+24G>A in and g.46474746C>T in were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition, transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups. Our findings demonstrate the role of differential expression and genetic variants of TGFβ-Smad pathway in CML. Decreased and levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.