Abstract
Clonal hematopoiesis (CH) is an early indicator of hematologic malignancies, driven by mutations in hematopoietic stem cells (HSCs) such as TET2 or P53. Recently ZBTB33 mutations have been implicated in myelodysplastic syndromes (MDS) and suggested as a driver of CH. However, the role of ZBTB33 in hematopoiesis and its causative involvement in CH remains unclear. We generated a Zbtb33-knockout mouse strain to elucidate its function in hematopoiesis and tumor growth. Our findings indicate that hematopoiesis in Zbtb33-knockout mice appeared grossly normal, and competitive bone marrow transplantation assays demonstrated that loss of Zbtb33 in HSCs did not confer expansional advantage. Introducing Zbtb33-mutation into Tet2- or P53-mutation background yielded no synergistical effects. Nevertheless, tumor-bearing experiments revealed that hematopoietic loss of Zbtb33 accelerated solid tumor growth. In summary, Zbtb33 knockout was insufficient to induce clonal hematopoiesis in mice but may play a role in tumor growth through the hematopoietic compartment.