Histone Deacetylase Inhibitors as Adjuvants for the Differentiation of Dendritic Cell from Leukemic Blasts.

Purpose. Recurrent cytogenetic abnormalities in leukemic blasts make these cells an attractive source of dendritic cells (DC) for leukemia-specific immune therapies. The purpose of this study was the evaluation of different histone deacetylase inhibitors in their potential to enhance the immunogenicity of leukemic DCs.

Methods. Leukemic blasts from 96 patients with acute lymphoblastic leukemia were cultured in two different cytokine combinations and either SAHA, valproic acid, isobutyramide or trichostatin A. Immune phenotype, T-cell allostimulatory capacities and cytotoxic responses were determined in DC generated after culture for one and two weeks.

Results. 71 of 96 blasts developed a typical DC morphology with 55 showing an upregulation of CD83, HLA-DR and costimulatory molecules like CD80 and CD86. The allostimulatory potential of the leukemic DCs was not influenced by the addition of HdI. DCs generated with cytokines and SAHA or valproic acid from TEL/AML1-positive blasts of patients with a t(12;21) translocation induced blast-specific cytotoxic T-cell responses in HLA-A matched T cells. The DC differentiability of TEL/AML1-negative blasts was not diminished by the use of HdI.

Conclusion. Histone deacetylase inhibitors could be used for the development of a dendritic cell-based anti-leukemia vaccine.