Hck, short for hematopoietic cell kinase, is a member of the Src-family of non-receptor tyrosine kinases. It is expressed in cells of hematopoietic origin, particularly myelomonocytic cells and B lymphocytes. Hck participates in multiple cell processes such as phagocytosis, adhesion, migration, and actin polymerization. It is also involved in signaling pathways related to cell regulation [2].

In kidney diseases, global or myeloid cell-specific Hck-knockout (KO) attenuates renal inflammation and fibrosis in unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (IRI) models. Hck-KO or Hck-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration, and Hck inhibits autophagy flux in macrophages by interacting with autophagy-related proteins [1].

In pancreatic ductal adenocarcinoma (PDAC), genetic ablation of Hck in myeloid cells impairs PDAC growth and metastasis, reduces the desmoplastic microenvironment, and enhances cytotoxic effector cell infiltration [3].

In acute myeloid leukemia (AML), Hck is highly expressed in leukemia stem cells (LSCs) compared to hematopoietic stem cells (HSCs). Knockdown of Hck leads to cell cycle arrest, decreasing the proliferation and colony formation of human AML cell lines, and Hck is required for leukemogenesis and leukemia maintenance in vivo and in vitro [4].

In conclusion, Hck plays crucial roles in various biological processes and disease conditions. The use of Hck KO mouse models has revealed its significance in renal inflammation and fibrosis, pancreatic cancer, and leukemia. These findings suggest that Hck could be a potential therapeutic target in these disease areas.