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

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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 ; Verjovski-Almeida, Sergio ; Traina, Fabiola ; Molinari, Alessio ; Botta, Maurizio ; Olalla Saad, Sara Teresinha

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1863, n. 2, p. 450-461, FEB 2017.
• Citações Web of Science: 3

Resumo

New drug development for neoplasm treatment is nowadays based on molecular targets that participate in the disease pathogenesis and tumor phenotype. Herein, we describe a new specific pharmacological hematopoietic cell kinase (HCK) inhibitor (iHCK-37) that was able to reduce PI3K/AKT and MAPK/ERK pathways activation after erythropoietin induction in cells with high HCK expression: iHCK-37 treatment increased leukemic cells death and, very importantly, did not affect normal hematopoietic stem cells. We also present evidence that HCK, one of Src kinase family (SFK) member, regulates early-stage erythroid cell differentiation by acting as an upstream target of a frequently deregulated pathway in hematologic neoplasms, PI3K/AKT and MAPK/ERK. Notably, HCK levels were highly increased in stem cells from patients with some diseases, as Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML), that are associated with ineffective erythropoiesis These discoveries support the exploration of the new pharmacological iHCK-37 in future preclinical and clinical studies. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 11/22376-7 - Investigação de vias desreguladas em mielodisplasia e leucemias agudas a partir de resultados prévios obtidos em microarranjos
• Beneficiário: Fernanda Marconi Roversi
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado