Background
Leukaemia stem cells (LSCs) are responsible for the initiation, maintenance, and recurrence of acute myeloid leukaemia (AML), an aggressive haematological malignancy associated with drug resistance and relapse. Identifying therapeutic LSC targets is critical to curing AML.
Conclusions
HCK maintains the self-renewal of leukaemia stem cells via CDK6 in AML and may be an ideal therapeutic target for eradicating LSCs without influencing normal haematopoiesis.
Methods
Bioinformatics databases were used to identify therapeutic LSC targets. The conditional knockout mice were used to analyse the role of HCK in leukaemogenesis or normal haematopoiesis. Colony-forming assays, cell counting, and flow cytometry were used to detect the viability and function of leukaemia cells. RT-PCR, western blotting, and RNA sequencing were used to detect mRNA and protein expression. Result: HCK is expressed at higher levels in LSCs than in haematopoietic stem cells (HSCs), and high HCK levels are correlated with reduced survival time in AML patients. Knockdown of HCK leads to cell cycle arrest, which