Transforming growth factor-ß1-Smad (TGF-ß1-Smad) pathway plays important role in differentiation, proliferation, apoptosis, and several other cellular processes. Many types of differentiating blood cells including activated lymphocytes and dendritic cells either produce TGFß1 or are responsive to it. As TGFß1 ligand binds to TGFB-Receptor II (TGFBR2), it dimerises and recruits TGFB-Receptor I (TGFBR1) that is being phosphorylated. This combination further phosphorylates R-Smads (Smad 2, 3) and Co-Smad (Smad 4). The resulting complex translocates to the nucleus and regulates the expression of target genes. Diversion of the pathway from normal conduct has implications in various diseases including several types of cancers. Previously we have submitted the sequencing results of important genes of this pathway (ECC15-3210). In this study, we analyzed expression of three important members of the pathway, ligand TGFß1, receptors TGFßR1 and TGFßR2 in 33 Chronic Myeloid Leukemia (CML) patients.
CML patients (n = 33) were recruited strictly according to inclusion criteria (Age: 18 + , Confirmed BCR-Abl by PCR and FISH test). Healthy individuals were also recruited as controls (n = 26). Transcript levels of both receptor genes were examined by Real-Time PCR. Beta Actin was used as endogenous gene. Levels of TGFß1 ligand in serum were analyzed by ELISA (DRG Diagnostics, Germany). Significance levels were calculated by Student T-test test using software SPSS (version 16.0).
TGFß1 protein levels were significantly up-regulated in patient (p = 0.005) compared to controls. This prompted us to examine levels of receptors TGFBR1 and TGFBR2 at transcript level in CML patients. We observed that TGFBR2 was down-regulated in more than 50% of patients and no significant change in 30% of patients. However no conclusive trend of expression in TGFBR1 was noted.
The results indicate that TGF-ß-Smad pathway is expected to play an important role in CML. This study is an ongoing study and increasing the sample size will help us to further define the role of TGF-ß-Smad pathway in CML
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All authors have declared no conflicts of interest.