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

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

Abstract

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

(6)

(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)

BERNUSSO, VANESSA ALINE; VIEIRA, KARLA P.; DUARTE, ADRIANA S. S.; LESCANO, CAROLINE HONAISER; MONICA, FABIOLA ZAKIA; VICENTE, CRISTINA PONTES; DE PAULA, ERICH VINICIUS; OLALLA SAAD, SARA TERESINHA; LAZARINI, MARIANA. eficiency of ARHGAP21 alters megakaryocytic cell lineage responses and enhances platelet hemostatic functio. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1868, n. 6, MAY 2021. (17/21801-2, 13/13022-2, 17/19674-2)

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. (17/19674-2)

MARIANA FERREIRA PISSARRA; CRISTIANE OKUDA TORELLO; SARA TERESINHA OLALLA SAAD; MARIANA LAZARINI. Evaluation of different protocols for culturing mesenchymal stem cells derived from murine bone marrow. Hematology, Transfusion and Cell Therapy, v. 44, n. 4, p. 560-566, 2022-12-12. (17/21801-2, 17/19674-2)

BERNUSSO, VANESSA ALINE; VIEIRA, KARLA P.; DUARTE, ADRIANA S. S.; LESCANO, CAROLINE HONAISER; MONICA, FABIOLA ZAKIA; VICENTE, CRISTINA PONTES; DE PAULA, ERICH VINICIUS; OLALLA SAAD, SARA TERESINHA; LAZARINI, MARIANA. Deficiency of ARHGAP21 alters megakaryocytic cell lineage responses and enhances platelet hemostatic function. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1868, n. 6, p. 13-pg., 2021-03-25. (17/19674-2, 13/13022-2, 17/21801-2)

LAZARINI, MARIANA; ASSIS-MENDONCA, GUILHERME ROSSI; MACHADO-NETO, JOAO AGOSTINHO; LATUF-FILHO, PAULO; BEZERRA, STEPHANIA MARTINS; VIEIRA, KARLA PRISCILA; SAAD, SARA TERESINHA OLALLA. Silencing of ARHGAP21, a Rho GTPase activating protein (RhoGAP), reduces the growth of prostate cancer xenografts in NOD/SCID mice. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1870, n. 4, p. 4-pg., 2023-02-17. (17/19674-2, 21/14630-2, 17/21801-2)

RAMOS, DEBORA FELICIA VIEIRA; MANCUSO, RUBIA ISLER; CONTIERI, BRUNA; DUARTE, ADRIANA; PAIVA, LUCIANA; CARRILHO, JEFERSON DE MELO; SAAD, SARA TERESINHA OLALLA; LAZARINI, MARIANA. Rac GTPases in acute myeloid leukemia cells: Expression profile and biological effects of pharmacological inhibition. Toxicology and Applied Pharmacology, v. 442, p. 12-pg., 2022-05-01. (17/19674-2, 17/21801-2)