Epigenetics of multiple myeloma after treatment with cytostatics and gamma radiation

Genetic and epigenetic changes in multiple myeloma (MM) correlate with the stage of the disease. Therefore, we investigated how cytostatics and gamma radiation influence MM-associated histone modifications. ChIP-PCR and ChIP-on-chip technologies were used to quantify H3K9 acetylation and H3K9 dimethylation at select loci in MM patients, lymphoblastoid ARH-77, and myeloma MOLP-8 cells. Genome-wide analysis revealed that the cytostatic, melphalan, increased H3K9 acetylation at multiple gene promoters in ARH-77 cells. Melphalan and gamma radiation also influenced histone modification of prognostically important c-myc and CCND1 genes in ARH-77 and MOLP-8 cells. Moreover, H3K9 acetylation at c-myc and CCND1 promoters was increased in individual MM patients after melphalan treatment. Western blotting revealed that these effects were accompanied by changes in c-MYC and cyclin D1 protein levels. Taken together, we showed that cytostatics significantly alter histone modification of tumor-related genes which is indispensable for understanding cancer therapies.