Role of the gut microbiota in hematopoietic homeostasis and leukemogenesis

Abstract

Recent studies have revealed that the gut microbiota play a critical role in the regulation of hematopoiesis at multiple stages. Accumulated evidence of the relationship between the clinical outcome of allogeneic hematopoietic stem cell transplantation and diversity of the microbiota demonstrates the importance of the microbiota in the physiological and pathological regulation of hematopoiesis. In addition, recent studies have shown that aberrant diet-related changes in the microbiota may cause abnormal hematopoiesis and contribute to the progression of myeloproliferative neoplasm in combination with RAS-MAPK activation. Ten-eleven translocation 2 (Tet2) mutation in myeloid cells causes dysfunction of the small-intestinal barrier, which leads to induction of preleukemic myeloproliferation. Proliferation of leukemia cells is associated with reduced insulin secretion and enhancement of insulin resistance, partly due to microbiota-derived metabolites. Thus, the microbiota affects normal and malignant hematopoiesis mediated by multiple factors. Further analyses may contribute to the identification of critical environmental factors, which may lead to the discovery of novel diagnostic and therapeutic strategies for hematopoietic neoplasms.