Monocytic differentiation induced by side-chain modified analogs of vitamin D in ex vivo cells from patients with acute myeloid leukemia

Leuk Res. 2014 May;38(5):638-47. doi: 10.1016/j.leukres.2014.03.009. Epub 2014 Mar 20.

Abstract

The differentiation-inducing potential of side-chain modified analogs of vitamins D, compared to the reference compound, 1,25-dihydroxyvitamin D3, was studied in blast cells from patients with acute myeloid leukemia and in cell lines. Analogs PRI-1906 and PRI-1907 showed increased cell-differentiation activities, PRI-1907 even at a very low concentration. Our study revealed a high variability of individual patients' blasts in their susceptibility to vitamin D analogs. The blasts of the patients with normal karyotype and with mutated NPM1 reacted to analogs with stronger differentiation than the blasts of the remaining patients, while the blasts with mutated FLT3 receptor reacted with weaker differentiation than the remaining blasts.

Keywords: 1 ;25-dihydroxyvitamin D(3); Acute myeloid leukemia; Blasts; Differentiation; Flow cytometry; Personalized anticancer therapy; Statistical analysis; Vitamin D analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation / drug effects*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Monocytes / cytology*
  • Mutation
  • Nucleophosmin
  • Vitamin D / analogs & derivatives*
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • NPM1 protein, human
  • Nucleophosmin
  • Vitamin D
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3