Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5501116 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2017 | 49 Pages |
Abstract
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.
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Authors
Fernanda Marconi Roversi, Fernando Vieira Pericole, João Agostinho Machado-Neto, Adriana da Silva Santos Duarte, Ana Leda Longhini, Flávia Adolfo Corrocher, Bruna Palodetto, Karla Priscila Ferro, Renata Giardini Rosa, Mariana Ozello Baratti,