Bone marrow microenvironment mediated drug resistance in Acute promyelocytic leukemia

About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. There are limited study available on the effect of leukemic cell interaction on stromal cells. We undertook a preliminary study to evaluate the changes induced by leukemic cells on stromal cells. In a gene expression profiling comparing HS-5 cells in co-culture with NB4 cells alone, 8456 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion, Cytokines, Wnt signalling in the stromal cells. The HS-5 cells were co-cultured with NB4 cells for 48 hours and the stromal cells were taken out after washing with PBS, characterized by flow cytometry to obstain a purity of more than 95% and subjected to RNA isolation. Similarly HS-5 cells alone were alone used as controls