BACKGROUND: Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective and dysplastic haemopoiesis. Previous studies in the lab have shown extensive apoptosis and high levels of transforming growth factor (TGF-beta) and tumor necrosis factor (TNF-alpha) in the stromal layer of MDS bone marrow. The current study focuses on the cytokines expressed in the bone marrow parenchymal cells. MATERIALS AND METHODS: Bone marrow aspirate from 5 normal donors and 26 patients with myelodysplastic syndromes were examined for mRNA expression of tumor necrosis factor alpha (TNF-alpha), macrophage colony stimulating factor (M-CSF), Flt-3 Ligand (Flt-3L), Flt-3 receptor(Flt-3 rec), interleukin 1 beta (IL 1 beta) and interleukin 1 receptor antagonist (IL-1 ra). RESULTS: Comparison of 26 MDS marrows with 5 normals showed a significantly higher value for Flt-3 rec and IL 1 beta (p = 0.031 and p = 0.031) in the former, while only Flt-1 beta rec was considerably higher (p = 0.016) in newly diagnosed patients. In previously diagnosed group, Flt-3 rec (p = 0.001), TNF-alpha (p = 0.04) and IL-1 beta (p = 0.016) were higher than normal while there was no statistically significant difference in the newly versus previously diagnosed MDS cases: CONCLUSION: mRNA expression of all six cytokines measured were considerably higher in MDS when compared to normal and that these levels tend to increase with disease duration. The precise source of these cytokines as well as their role in MDS pathogenesis remains to be determined, but this study confirms our previous reports that there is no dearth of cytokines in these bizarre myelosuppressive states.
BACKGROUND:Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective and dysplastic haemopoiesis. Previous studies in the lab have shown extensive apoptosis and high levels of transforming growth factor (TGF-beta) and tumor necrosis factor (TNF-alpha) in the stromal layer of MDS bone marrow. The current study focuses on the cytokines expressed in the bone marrow parenchymal cells. MATERIALS AND METHODS: Bone marrow aspirate from 5 normal donors and 26 patients with myelodysplastic syndromes were examined for mRNA expression of tumor necrosis factor alpha (TNF-alpha), macrophage colony stimulating factor (M-CSF), Flt-3 Ligand (Flt-3L), Flt-3 receptor(Flt-3 rec), interleukin 1 beta (IL 1 beta) and interleukin 1 receptor antagonist (IL-1 ra). RESULTS: Comparison of 26 MDS marrows with 5 normals showed a significantly higher value for Flt-3 rec and IL 1 beta (p = 0.031 and p = 0.031) in the former, while only Flt-1 beta rec was considerably higher (p = 0.016) in newly diagnosed patients. In previously diagnosed group, Flt-3 rec (p = 0.001), TNF-alpha (p = 0.04) and IL-1 beta (p = 0.016) were higher than normal while there was no statistically significant difference in the newly versus previously diagnosed MDS cases: CONCLUSION: mRNA expression of all six cytokines measured were considerably higher in MDS when compared to normal and that these levels tend to increase with disease duration. The precise source of these cytokines as well as their role in MDS pathogenesis remains to be determined, but this study confirms our previous reports that there is no dearth of cytokines in these bizarre myelosuppressive states.
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: Tony A Navas; Mani Mohindru; Myka Estes; Jing Ying Ma; Lubomir Sokol; Perry Pahanish; Simrit Parmar; Edwin Haghnazari; Li Zhou; Robert Collins; Irene Kerr; Aaron N Nguyen; Yin Xu; Leonidas C Platanias; Alan A List; Linda S Higgins; Amit Verma Journal: Blood Date: 2006-08-29 Impact factor: 22.113
Authors: I Gañán-Gómez; Y Wei; D T Starczynowski; S Colla; H Yang; M Cabrero-Calvo; Z S Bohannan; A Verma; U Steidl; G Garcia-Manero Journal: Leukemia Date: 2015-03-12 Impact factor: 11.528
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: Tony Navas; Li Zhou; Myka Estes; Edwin Haghnazari; Aaron N Nguyen; Yongkai Mo; Perry Pahanish; Mani Mohindru; Tim Cao; Linda S Higgins; Leonidas C Platanias; Alan List; Amit Verma; T Bhagat; S Gajavelli; S Kambhampati Journal: Leuk Lymphoma Date: 2008-10
Authors: Wolf C Prall; Akos Czibere; Franck Grall; Dimitrios Spentzos; Ulrich Steidl; Aristoteles Achilles Nikolaus Giagounidis; Andrea Kuendgen; Hasan Otu; Astrid Rong; Towia A Libermann; Ulrich Germing; Norbert Gattermann; Rainer Haas; Manuel Aivado Journal: Int J Hematol Date: 2009-01-20 Impact factor: 2.490