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

Maria Fernanda Lopes Carvalho; Bruna Oliveira de Almeida; Maura Lima Pereira Bueno; Hugo Passos Vicari; Keli Lima; Eduardo Magalhães Rego; Fernanda Marconi Roversi; João Agostinho Machado-Neto

doi:10.1016/j.htct.2023.11.007

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

Hematol Transfus Cell Ther. 2023 Dec 31:S2531-1379(23)02607-X. doi: 10.1016/j.htct.2023.11.007. Online ahead of print.

Authors

Maria Fernanda Lopes Carvalho¹, Bruna Oliveira de Almeida¹, Maura Lima Pereira Bueno², Hugo Passos Vicari¹, Keli Lima³, Eduardo Magalhães Rego⁴, Fernanda Marconi Roversi⁵, João Agostinho Machado-Neto⁶

Affiliations

¹ Institute of Biomedical Sciences, University of São Paulo (USP), SP, Brazil.
² Hematology and Transfusion Medicine Center, University of Campinas, Hemocentro-UNICAMP, Campinas, São Paulo, Brazil.
³ Institute of Biomedical Sciences, University of São Paulo (USP), SP, Brazil; Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.
⁴ Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.
⁵ Hematology and Transfusion Medicine Center, University of Campinas, Hemocentro-UNICAMP, Campinas, São Paulo, Brazil; Department of Surgery Division Emory University, Atlanta, GA, USA.
⁶ Institute of Biomedical Sciences, University of São Paulo (USP), SP, Brazil. Electronic address: jamachadoneto@usp.br.

PMID: 38326180
DOI: 10.1016/j.htct.2023.11.007

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 provide new insights into HCK biological functions, prognosis, and response to antineoplastic agents.

Keywords: Acute myeloid leukemia; Bioinformatics; Clinical outcomes; Hematopoietic cell kinase; Pharmacology.