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Bone marrow micro-environment mediated drug resistance in Acute promyelocytic leukemia

ABSTRACT: 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. We undertook a preliminary study to evaluate the role of EM-DR to ATO in APL. In direct co-culture (contact dependent system) of malignant promyelocyte with stromal cells, the stromal cells gave a significant protective effect against ATO at different concentrations used (1 to 8 μmol; NB4 (APL cell line) In a gene expression profiling comparing NB4 cells in co-culture with NB4 cells alone, 1846 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion (ITGB1, ITGB2, ITGB7, etc.), Cytokines (IL-6, IL-8, IL-18, CCL2, CCL10, etc.) Wnt signalling (Wnt5a, Wnt11, NFATC4, etc,) NF-kB pathway (ICAM1, BIRC2, BIRC3, XIAP1, etc.) in the leukemic cells. The NF-kB pathway has been validated using real time PCR which correlated with the genes being differentially regulated in NB4 cells co-cultured in stroma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73157 | GEO | 2016/09/01

SECONDARY ACCESSION(S): PRJNA296065

REPOSITORIES: GEO

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Bone marrow micro-environment mediated drug resistance in Acute promyelocytic leukemia

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