Novel inhibitor of hematopoietic cell kinase as a potential therapeutic agent for acute myeloid leukemia

Comprehensive analysis of the HCK gene in myeloid neoplasms: Insights into biological functions, prognosis, and response to antineoplastic agents

“…In a previous study, the pharmacological HCK inhibition, using iHCK-37, potentiated the reduction in cell viability induced by 5-azacytidine in KG1a, HL-60, and K-562 leukemia cells. 11 In addition, iHCK-37 increased 5-azacytidine-induced apoptosis in CD34 + cells isolated from de novo AML patients. 11 …”

“… 11 In addition, iHCK-37 increased 5-azacytidine-induced apoptosis in CD34 + cells isolated from de novo AML patients. 11 …”

“…Our research group has been characterizing the biological functions of the hematopoietic cell kinase (HCK), a proto-oncogene encoding a protein tyrosine kinase of the Src family, and assessing its potential as a pharmacological target. 9 , 10 , 11 The HCK gene was identified as highly expressed in CD34 + cells obtained from patients with myelodysplastic syndrome (MDS) using a microarray assay 12 and in patients with de novo AML. 9 Genetic (shRNA) or pharmacological inhibition of HCK demonstrated relevant antileukemic effects in vitro and ex vivo cell models.…”

Nuclear factor Nrf2 promotes glycosidase OGG1 expression by activating the AKT pathway to enhance leukemia cell resistance to cytarabine

“…For example, exo-miR-7-5p derived from BM mesenchymal stem cells promotes AML cell apoptosis by blocking the phosphorylation of PI3K/AKT/mammalian target of rapamycin signaling ( 42 ). Hematopoietic kinase inhibitors combined with 5-azacytidine or Ara-C can decrease AKT/extracellular signal–regulated kinase phosphorylation and increase the expressions of apoptotic proteins ( 43 ). Moreover, some studies have demonstrated that the continuous activation of PI3K/AKT signaling may be the cause of AML drug resistance ( 30 ).…”

The antitumor effects of WNT5A against hematological malignancies

“…Peripheral blood mononuclear cells (PBMCs) were isolated using standard Ficoll‐Hypaque (Sigma‐Aldrich). CD34‐positive cells were isolated using magnetically activated cell sorting isolation kit (Miltenyi Biotec) and cultured in X‐Vivo20 media (Lonza) with 20% FBS, 100 ng/mL Stem Cell Factor (SCF), 100 ng/mL Fmsrelated tyrosine kinase 3 ligand (FLT3L), 100 ng/mL Thrombopoietin (TPO), 60 ng/mL interleukin‐3 (IL‐3) and 10 ng/mL interleukin‐6 (IL‐6) (PrepoTech), and maintained at 37 °C and 5% CO 2 (Roversi et al 2022).…”