Genomic And Epigenetic Effects Of Dna Methyltransferase Inhibition In Acute Lymphoblastic Leukemia

Background: Children with acute lymphoblastic leukemia (ALL) who relapse are more resistant to chemotherapy. We have previously identified a unique gene expression signature associated with relapsed leukemic blasts and showed that relapse samples have higher level of CpG methylation compared to diagnosis. We also demonstrated that treatment with DNMT inhibitor, decitabine, alone or in combination with the HDAC inhibitor, vorinostat restored blast chemosensitivity in vitro . These observations led to the hypothesis that global methylation status is a key regulator of drug resistance.