Characterization of FMNL1 in the leukemic process and normal hematopoiesis

• Grant number: 16/04570-4
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2017
• End date: August 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Maria Bergamo Favaro
• Grantee: Patricia Maria Bergamo Favaro
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Marcelo Mendes Brandao ; Mariana Lazarini ; Sara Teresinha Olalla Saad

Abstract

FMNL1 is predominantly expressed in peripheral blood leukocytes, spleen and thymus. However, this protein is highly expressed in several hematologic malignancies. We have recently demonstrated the role of FMNL1 in proliferation, and migration cells in Namalwa cell line (Burkitt's lymphoma), which suggests its contribution to the leukemogenesis. Next, our group conducted a microarray assay in Namalwa cells, comparing the gene regulation between cells inhibited for FMNL1 expression and their control (preliminary data). Through bioinformatics analysis, we selected nine genes for validation, with the majority involved in mobility and tumor metastasis. Thus, our hypothesis is that FMNL1 participate in the process of metastasis and our objective is to evaluate the FMNL1 functions in models in vitro and in vivo. FMNL1 also participates in various functions of normal hematopoietic cells. Data in the literature indicate the importance of mDia1, another DRF formin, in the regulation of pro-platelet formation. To better understand the FMNL1 roles in megakaryocytic differentiation, we used an established model of megakaryocytic differentiation in K562 cells and PMA. An increase of about 15 times the FMNL1 expression was observed, after treatment with PMA (preliminary data). Thus, our second hypothesis of the study is that FMNL1 participate in megakaryopoiesis process. Our second objective is to study the FMNL1 function in megakaryocytic differentiation, using both cell line model as well as primary CD34 + cells. (AU)