regulates fatty acid metabolism and proliferation at the Pre-B cell stage during B cell development.

During B cell development in bone marrow, large precursor B cells (large Pre-B cells) proliferate rapidly, exit the cell cycle, and differentiate into non-proliferative (quiescent) small Pre-B cells. Dysregulation of this process may result in the failure to produce functional B cells and pose a risk of leukemic transformation. Here, we report that AT rich interacting domain 5B (), a B cell acute lymphoblastic leukemia (B-ALL) risk gene, regulates B cell development at the Pre-B stage. In both mice and humans, we observed a significant upregulation of expression that initiates at the Pre-B stage and is maintained throughout later stages of B cell development. In mice, deletion of and exhibited a significant reduction in the proportion of immature B cells but an increase in large and small Pre-B cells. inhibition also led to an increase in proliferation of both Pre-B cell populations. Metabolic studies in mouse and human bone marrow revealed that fatty acid uptake peaked in proliferative B cells then decreased during non-proliferative stages. We showed that ablation enhanced fatty acid uptake and oxidation in Pre-B cells. Furthermore, decreased expression was observed in tumor cells from B-ALL patients when compared to B cells from non-leukemic individuals. In B-ALL patients, expression below the median was associated with decreased survival particularly in subtypes originating from Pre-B cells. Collectively, our data indicated that regulates fatty acid metabolism and proliferation of Pre-B cells in mice, and reduced expression of in humans is a risk factor for B cell leukemia.