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Study of Rho family of GTPases in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Grant number: 17/19674-2
Support type:Regular Research Grants
Duration: September 01, 2018 - November 30, 2020
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Mariana Lazarini
Grantee:Mariana Lazarini
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Assoc. researchers: Anne Ridley ; Sara Teresinha Olalla Saad


Acute myeloid leukemia (AML) is a blood cell cancer that can start from the progression of myelodysplastic syndromes (MDS). Bone marrow cells from MDS and AML patients present genomic alterations that result in gene expression changes, leading to increased proliferation and decreased differentiation and apoptosis. To understand how MDS and AML progress, it is therefore important to identify gene expression changes and determine how they alter myeloid cell properties. Rho GTPases are intracellular signaling molecules that play central roles in cell proliferation, survival and migration through the regulation of cytoskeleton. The human genome contains twenty Rho GTPase coding genes, of which RhoA, Rac1 and Cdc42 are the most studied. These three proteins participate in hematopoiesis regulation and their deregulation has been found in myeloid neoplasia. However, little is known about the roles of the other Rho GTPase members in myeloid neoplasia. We propose that Rho GTPases are deregulated and contribute to MDS and AML pathogenesis. The aim of this proposal is to evaluate the expression of Rho GTPases in bone marrow cells from MDS and AML patients and associate with clinical outcome. Based on gene expression analysis, some Rho GTPases will be selected and their functions will be investigated in hematopoietic cells. Results from this study will generate new insights into how Rho GTPase signaling contributes to leukemia. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CONTIERI, BRUNA; DUARTE, BRUNO KOSA LINO; LAZARINI, MARIANA. Updates on DNA methylation modifiers in acute myeloid leukemia. ANNALS OF HEMATOLOGY, v. 99, n. 4 FEB 2020. Web of Science Citations: 0.

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