Disease-stabilizing treatment based on all-trans retinoic acid and valproic acid in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive malignancy that can only be cured by intensive therapy. However, many elderly and unfit patients cannot receive such treatment due to an unacceptable risk of treatment-related morbidity and mortality. Disease-stabilizing therapy is then the only possible strategy, one alternative being treatment based on all-trans retinoic acid (ATRA) combined with the histone deacetylase inhibitor valproic acid and possibly low-toxicity conventional chemotherapy. Primary AML cells were derived from patients included in two clinical studies of treatment based on ATRA plus valproic acid; low toxicity chemotherapy (low-dose cytarabine, hydroxyurea, 6-mercaptopurin) was also allowed. Pretreatment leukemic cells were analyzed by mutation profiling of 54 genes frequently mutated in myeloid malignancies and by global gene expression profiling before and during in vivo treatment.