CONTEXT: Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS. OBJECTIVE: To determine if certain polymorphisms in the tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) cytokines are overrepresented in a cohort of patients with MDSs. DESIGN: DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFalpha and 2 in TGFbeta1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database. RESULTS: In our MDS population, the -308A/A genotype of the TNFalpha gene and the TGFbeta1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population. CONCLUSIONS: Polymorphisms associated with increased expression in the cytokines TNFalpha and TGFbeta1 are overrepresented in the MDS population suggesting that increased TNF-alpha and TGF-beta1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.
CONTEXT: Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS. OBJECTIVE: To determine if certain polymorphisms in the tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) cytokines are overrepresented in a cohort of patients with MDSs. DESIGN: DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFalpha and 2 in TGFbeta1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database. RESULTS: In our MDS population, the -308A/A genotype of the TNFalpha gene and the TGFbeta1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population. CONCLUSIONS: Polymorphisms associated with increased expression in the cytokines TNFalpha and TGFbeta1 are overrepresented in the MDS population suggesting that increased TNF-alpha and TGF-beta1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.
Authors: Li Zhou; Christine McMahon; Tushar Bhagat; Cristina Alencar; Yiting Yu; Melissa Fazzari; Davendra Sohal; Christoph Heuck; Krishna Gundabolu; Chun Ng; Yongkai Mo; Wa Shen; Amittha Wickrema; Guanghui Kong; Ellen Friedman; Lubomir Sokol; Ioannis Mantzaris; Giannis Mantzaris; Andrea Pellagatti; Jacqueline Boultwood; Leonidas C Platanias; Ulrich Steidl; Lei Yan; Jonathan M Yingling; Michael M Lahn; Alan List; Markus Bitzer; Amit Verma Journal: Cancer Res Date: 2010-12-28 Impact factor: 12.701
Authors: Li Zhou; Aaron N Nguyen; Davendra Sohal; Jing Ying Ma; Perry Pahanish; Krishna Gundabolu; Josh Hayman; Adam Chubak; Yongkai Mo; Tushar D Bhagat; Bhaskar Das; Ann M Kapoun; Tony A Navas; Simrit Parmar; Suman Kambhampati; Andrea Pellagatti; Ira Braunchweig; Ying Zhang; Amittha Wickrema; Satyanarayana Medicherla; Jacqueline Boultwood; Leonidas C Platanias; Linda S Higgins; Alan F List; Markus Bitzer; Amit Verma Journal: Blood Date: 2008-05-12 Impact factor: 22.113
Authors: J X Zou; D E Rollison; D Boulware; D-T Chen; E M Sloand; L V Pfannes; J J Goronzy; F Bai; J S Painter; S Wei; D Cosgrove; A F List; P K Epling-Burnette Journal: Leukemia Date: 2009-03-12 Impact factor: 12.883