JNK pathway as a regulator of chemo‑resistancein acute myeloid leukemia (AML)

The pathways and robust deregulated gene signatures involvedin AML chemo-resistance are not fully understood. Multiplesubgroups of AMLs which are under treatment of variousregimens seem to have the similar regulatory gene(s) orpathway(s) related to their chemo-resistance phenotype. Inthis study using a gene set enrichment approach, deregulatedgenes and pathways associated with relapse after chemotherapywas investigated in AML samples. Five AML libraries compiledfrom GEO and ArrayExpress repositories were used toidentify significantly differentially expressed genes betweenchemo-resistance and chemo-sensitive groups. Functional andpathway enrichment analysis of deferentially expressed geneswas performed to assess molecular mechanisms related to AMLchemotherapeutic resistance. A total of ۳۴ genes were selectedto be differentially expressed in the chemoresistance comparedto the chemo-sensitive group. Among the genes selected, c-Jun,AKT۳, ARAP۳, GABBR۱, PELI۲, and SORT۱ are involved inneurotrophin, estrogen, cAMP, and Toll-like receptor signalingpathways. All these pathways are located upstream and regulatethe JNK signaling pathway which functions as a key regulatorof cellular apoptosis. Our expression data are in favor of suppressionof the JNK pathway, which could induce pro-apoptoticgene expression as well as down-regulation of survival factors,introducing this pathway as a key regulator of drug-resistancedevelopment in AML.

کلیدواژه ها:

Acute myeloid leukemia ، Gene expression ، Chemoresistance ، JUNK pathway