Physical interaction between BAALC and DBN1 induces chemoresistance in leukemia

Abstract

BAALC is identified as a leukemia-associated gene and is highly expressed in CD34-positive hematopoietic stem cells. High BAALC expression is associated with poor prognosis in several types of acute myeloid leukemia. We explored binding partner proteins of BAALC by means of mass spectrometry and analyzed biological properties of BAALC-expressing leukemic cells. We found that BAALC physically interacts with DBN1, which is an actin-binding protein and promotes cell adhesion and mobility by forming cell membrane spines during cell-cell interactions. Drebrin1 downregulation impeded cell adhesion to bone marrow stromal cells, resulting in improvement of sensitivity to cytarabine. Taken together, our findings suggest that BAALC-DBN1 interaction contributes to the anchoring of BAALC-expressing cells in the bone marrow, which in turn leads to resistance to cytotoxic drugs. Therefore, the BAALC-DBN1 interaction provides us with an opportunity to overcome the chemotherapy resistance in BAALC-activated leukemia via functional blockage of these genes.