GTPase regulator associated with the focal adhesion kinase (GRAF) transcript was down-regulated in patients with myeloid malignancies
نویسندگان
چکیده
BACKGROUND GTPase regulator associated with the focal adhesion kinase (GRAF), a putative tumor suppressor gene, is found inactivated in hematopoietic malignancies by either genetic or epigenetic abnormalities. However, the expression level of GRAF gene has not yet been studied in leukemia. The aim of this study was to investigate the expression level of GRAF gene in those patients with myeloid malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML). METHODS The expression levels of GRAF transcript were determined in 94 patients using real-time quantitative PCR (RQ-PCR). Clinical and laboratory data of these patients were collected and analyzed. RESULTS The significantly decreased level of GRAF transcript was observed in three myeloid malignancies compared to controls. Within AML, there was no difference in the level of GRAF transcript among different FAB subtypes (P > 0.05). Difference was not observed in the amount of GRAF mRNA between CML at chronic phase and controls. As CML progressed, GRAF transcript significantly decreased. In MDS, three cases with 5q deletion had lower GRAF transcript than four without 5q deletion (median 0.76 vs 2.99) (P > 0.05). CONCLUSION our results demonstrate that the GRAF transcript is decreased in myeloid malignancies.
منابع مشابه
Down regulation of GTPase regulator associated with the focal adhesion kinase (GRAF) gene expression in patients with acute myeloblastic leukemia
Introduction: GTPase regulator associated with focal adhesion kinase (GRAF) is a recently identified GTPase activating protein that has the tumor suppressor properties. However, the expression level of GRAF in leukemia had received less attention. The main purpose of this research was the evaluating of the expression level of GRAF in patients with acute myeloid leukemia (AML). Materials and met...
متن کاملارزیابی میزان بیان ژن GRAF در بیماران B-ALL مراجعه کننده به بیمارستانهای مشهد و ارتباط آن با یافتههای آزمایشگاهی و بالینی بیماران
Background and Objective: Acute lymphoblastic leukemia is a disorder caused by the proliferation of malignant immature lymphoid cells. GRAF (GTPase regulator associated with focal adhesion kinase) which acts as a tumor suppressor gene is disabled in hematologic malignancies due to genetic and epigenetic abnormalities. In this study, GRAF gene expression was inspected in patients with B-ALL. ...
متن کاملStructure of the BH domain from graf and its implications for Rho GTPase recognition.
Cellular signaling by small G-proteins is down-regulated by GTPase-activating proteins (GAPs), which increase the rate of GTP hydrolysis. The GTPase regulator associated with focal adhesion kinase (Graf) exhibits GAP activity toward the RhoA and Cdc42 GTPases, but is only weakly active toward the closely related Rac1. We determined the crystal structure of a 231-residue fragment of Graf (GrafGA...
متن کاملFocal Adhesion Kinase (FAK) Involvement in Human Endometrial Remodeling During the Menstrual Cycle
Background: Endometrial remodeling occurs during each menstrual cycle in women. Reports have shown that, in a variety of cell types, processes such as proliferation, signaling complex formation and extra cellular matrix remodeling require a cytoplasmic tyrosine kinase, focal adhesion kinase (FAK). The present study has focused on the expression pattern of FAK in human endometrium during the men...
متن کاملCytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho.
Graf, the GTPase regulator associated with focal adhesion kinase was previously shown to have GAP activity for &Rgr; A and Cdc42 in vitro (Hildebrand et al 1996 Mol. Cell Biol. 16: 3169-3178). In this study we sought to determine whether Graf acted at the level of Cdc42, Rho, or both in vivo and whether Graf was a signal terminator or transducer for these proteins. Microinjection of Graf cDNA i...
متن کامل