Qian et al. Journal of Experimental & Clinical Cancer Research 2010, 29:111 http://www.jeccr.com/content/29/1/111 R E S E A R C H Open Access GTPase regulator associated with the focal adhesion kinase (GRAF) transcript was down- regulated in patients with myeloid malignancies Zhen Qian1, Jun Qian1*, Jiang Lin1, Dong-ming Yao1, Qin Chen1, Run-bi Ji1, Yun Li1, Gao-fei Xiao1, Jian-yong Li2 Abstract 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. Background Focal adhesion kinase (FAK), a non-receptor tyrosine kinase that resides at the sites of integrin clustering [1], plays an important role in the modulation of cell growth, proliferation, survival and migration [2]. Recently, FAK has been found to be overexpressed and/ or constitutively activated and correlated with increased motility, invasiveness, and proliferation of neoplastic cells of various tissue types [2]. Two published articles revealed that aberrant expression of FAK was observed in CD34+ leukemic cells and associated with enhanced blast migration, increased cellularity and poor prognosis [3,4]. Le et al showed that FAK silencing inhibited leu- kemogenesis in BCR/ABL-transformed hematopoietic cells [5]. Tyner et al also identified FAK as one of thera- peutic molecular targets in acute myeloid leukemia (AML) [6]. * Correspondence: qianjun0007@hotmail.com 1Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, China Full list of author information is available at the end of the article FAK protein is composed of an N-terminal FERM domain, a central kinase domain, and a C-terminal domain that includes the focal adhesion targeting (FAT) sequence responsible for FAK’s localization to focal adhesions. Both the N-terminal and C-terminal domains have been shown to mediate FAK interaction with a variety of other proteins critical for activation of FAK by integrins or other cell surface receptors as well as FAK regulation of different cellular functions [2]. GTPase regulator associated with focal adhesion kinase (GRAF) is a newly identified protein specifically binding to the proline-rich region in the COOH termi- nus of FAK and negatively regulates the small GTP- binding protein RhoA, which is well known for its growth-promoting effect in RAS-mediated malignant transformation [7,8]. GRAF gene is located at chromo- some 5q31 and its protein is ubiquitously expressed in various tissues [9]. Mutations and deletions of GRAF gene were found in some cases with AML or myelodys- plastic syndrome (MDS) with a deletion 5q [9]. Further- more, Bojesen et al [10] found that GRAF gene © 2010 Qian et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.