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

Author(s)

Carvalho, Maria Fernanda Lopes ; de Almeida, Bruna Oliveira ; Bueno, Maura Lima Pereira ; Vicari, Hugo Passos ; Lima, Keli ; Roversi, Fernanda Marconi ; Machado-Neto, Joao Agostinho

• Document type: Journal article
• Source: Hematology, Transfusion and Cell Therapy; v. 46, n. 3, p. 10-pg., 2024-06-08.

Abstract

Myeloid neoplasms result from molecular alterations in hematopoietic stem cells, with acute myeloid leukemia (AML) being one of the most aggressive and with a poor prognosis. Hematopoietic cell kinase (HCK) is a proto-oncogene that encodes a protein-tyrosine kinase of the Scr family, and it is highly expressed in AML. The present study investigated HCK expression in normal hematopoietic cells across myeloid differentiation stages and myeloid neoplasm patients. Within the AML cohort, we explored the impact of HCK expression on clinical outcomes and its correlation with clinical, genetic, and laboratory characteristics. Furthermore, we evaluated the association between HCK expression and the response to antineoplastic agents using ex vivo assay data from AML patients. HCK expression is higher in differentiated subpopulations of myeloid cells. High HCK expression was observed in patients with chronic myelomonocytic leukemia, chronic myeloid leukemia, and AML. In patients with AML, high levels of HCK negatively impacted overall and disease-free survival. High HCK expression was also associated with worse molecular risk groups and white blood cell count; however, it was not an independent prognostic factor. In functional genomic analyses, high HCK expression was associated with several biological and molecular processes relevant to leukemogenesis. HCK expression was also associated with sensitivity and resistance to several drugs currently used in the clinic. In conclusion, our analysis confirmed the differential expression of HCK in myeloid neoplasms and its potential association with unfavorable molecular risks in AML. We also (AU)

• FAPESP's process: 20/12842-0 - Impact of genetic ancestry on development, molecular characteristics and clinical outcome in adult patients with Acute Lymphoblastic Leukemia
• Grantee: Keli Cristina de Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/11038-8 - Investigation of ANKHD1-related signaling pathways and biological processes in Stomach Cancer
• Grantee: Bruna Oliveira de Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/14505-6 - Investigation of the antineoplastic potential of pharmacological inhibition of ezrin in solid tumors: gastric adenocarcinoma and cervical carcinoma
• Grantee: Maria Fernanda Lopes Carvalho
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/11606-3 - Investigation of the antineoplastic effects of novel PIP4K2 and HDAC inhibitors in hematologic malignancies
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/01460-1 - Investigation of the antineoplastic potential of new drugs that modulate microtubule dynamics in Acute Myeloid Leukemia
• Grantee: Hugo Passos Vicari
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)