Investigation deregulated pathways in myelodysplasia and acute leukemia from previous results obtained using microarray

• Grant number: 11/22376-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2012
• End date: July 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Fernanda Marconi Roversi
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/51959-0 - Biology of neoplastic diseases of bone marrow, AP.TEM

Abstract

Myelodysplastic syndromes (MDS), are a heterogenic group of hematopoietic disorders caused by changes in pluripotent cells, common in the elderly, and a high rate of progression to acute myeloid leukemias (AML). These syndromes are characterized by ineffective hematopoiesis resulting in present dysplasia, impaired differentiation and peripheral blood cytopenias and result from multiple changes in the bone marrow stem cells that determine the differentiation deregulation and apoptosis of hematopoietic cells. There is no specific treatment for MDS, and the bone marrow transplantation corresponds to the unique alternative healing, but it is not applicable for most patients.. These syndromes have been described less than three decades and the molecular mechanisms involved in its pathogenesis have been elucidated only recently. In recent years a crescent interest has been given to the interaction of the progenitor cells with the stromal bone marrow, called hematopoietic niches. There are several indications that the curative treatment of diseases is correlated with interaction and mobilization of the quiescent cells. Microarray results of our research group have identified two particular interesting genes that could be involved in the physiopathology of MDS: Hematopoietic cell kinase genes (HCK) and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which are relate to changes in tumor environment of different cancer and the hematopoiesis regulation. The HCK, whose expression is specific for hematopoietic cells, showed increased expression in CD34+ cells from patients with MDS and possibly participates in transduction processes signaling related to the self-renewal, differentiation dysfunction and increased apoptosis in the hematopoietic MDS cells. The SPINT2, is an inhibitor of HGF production, and an inducer of SDF-1 secretion, which is related to angiogenesis and apoptosis in MDS. This gene is related to solid invasive tumors and was hipoexpressed in stromal cells of patients with MDS. Given the absence of data in the literature, this study aims to investigate the function of HCK and SPINT2 in the biology of Myelodysplastic Syndromes and Acute Myeloid Leukemia.

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)

ROVERSI, FERNANDA MARCONI; PERICOLE, FERNANDO VIEIRA; MACHADO-NETO, JOAO AGOSTINHO; SANTOS DUARTE, ADRIANA DA SILVA; LONGHINI, ANA LEDA; CORROCHER, FLAVIA ADOLFO; PALODETTO, BRUNA; FERRO, KARLA PRISCILA; ROSA, RENATA GIARDINI; BARATTI, MARIANA OZELLO; et al. Hematopoietic cell kinase (HCK) is a potential therapeutic target for dysplastic and leukemic cells due to integration of erythropoietin/PI3K pathway and regulation of erythropoiesis HCK in erythropoietin/PI3K pathway. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1863, n. 2, p. 450-461, FEB 2017. (11/22376-7)

ROVERSI, FERNANDA MARCONI; CURY, NATHALIA MORENO; LOPES, MATHEUS RODRIGUES; FERRO, KARLA PRISCILA; MACHADO-NETO, JOAO AGOSTINHO; ALVAREZ, MARISA CLAUDIA; DOS SANTOS, GABRIELA PEREIRA; ROSA, RENATA GIARDINI; LONGHINI, ANA LEDA; SANTOS DUARTE, ADRIANA DA SILVA; et al. Up-regulation of SPINT2/HAI-2 by Azacytidine in bone marrow mesenchymal stromal cells affects leukemic stem cell survival and adhesion. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v. 23, n. 2, p. 1562-1571, FEB 2019. (11/22376-7)

ROVERSI, FERNANDA MARCONI; LOPES, MATHEUS RODRIGUES; MACHADO-NETO, JOAO AGOSTINHO; LONGHINI, ANA LEDA F.; SANTOS DUARTE, ADRIANA DA SILVA; BARATTI, MARIANA OZELLO; PALODETTO, BRUNA; CORROCHER, FLAVIA ADOLFO; PERICOLE, FERNANDO VIEIRA; CAMPOS, PAULA DE MELO; et al. Serine Protease Inhibitor Kunitz-Type 2 Is Downregulated in Myelodysplastic Syndromes and Modulates Cell-Cell Adhesion. STEM CELLS AND DEVELOPMENT, v. 23, n. 10, p. 1109-1120, MAY 15 2014. (11/22376-7)