Abstract 5201: Identification of growth factors that promote the proliferation and drug resistance of human primary acute B lymphoblastic cells

Abstract

Abstract Bone marrow mesenchymal stem cells (BMMSCs) contribute the survival, expansion, and drug resistance of leukemic cells. However, how BMMSCs promote the proliferation and drug resistance of leukemia remains to be poorly understood. Here, we derived a BM-derived stromal cell line that supported unlimited growth of human primary acute B lymphoblastic leukemic cells (B-ALL) by physical contacts with B-ALL cells and secreting growth factors. Nevertheless, its capacity of promoting primary B-ALL proliferation was abolished once the cell line was induced to differentiate into adipocytes. In xenograft models, we demonstrate that the presence of adipocytes suppressed the engraftment of primary B-ALL cells while the decrease of adipocytes enhanced the reconstitution of B-ALL. Consistently, we observed that the increase of numbers and diameters of adipocytes was correlated with remission after chemotherapy treatments in B-ALL patients. By comparing the global transcription profiles between the BM stromal cells and the adipocytes that were derived from the cell line, we identified a combination of cytokines and adherent proteins that were able to support the long-term growth of human primary B-ALL cells and desensitize them to chemotherapy drugs in a stromal-free culture condition. Furthermore, we showed that the PI3K/AKT pathways were involved in chemotherapy-induced resistance because targeting these signaling pathways increased the chemotherapy sensitivity of B-ALL in xenografts. Collectively, our results uncovered the mechanisms of BMMSCs supporting the survival, expansion, and drug resistance of human B-ALL cells. Citation Format: Peng Li, Zhiwu Jiang. Identification of growth factors that promote the proliferation and drug resistance of human primary acute B lymphoblastic cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5201.