Differentiation of acute myeloid leukemia (AML) cells with ATRA reduces 18F-FDG uptake and increases sensitivity towards ABT-737-induced apoptosis

Leuk Lymphoma. 2021 Mar;62(3):630-639. doi: 10.1080/10428194.2020.1839648. Epub 2020 Nov 3.

Abstract

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow, comprising various subtypes. We have investigated seven different AML cell lines that showed different sensitivities toward the inducer of apoptosis ABT-737, with IC50 concentrations ranging from 9.9 nM to 1.8 µM. Besides, the AML cell lines revealed distinct differences in 18F-FDG uptake ranging from 4.1 to 11.0%. Moreover, the Pearson coefficient (0.363) suggests a moderate correlation between 18F-FDG uptake and the IC50 values of ABT-737. Differentiation of the AML cell lines NB-4 and AML-193 with all-trans-retinoic-acid (ATRA) induced a significant increase in sensitivity towards ABT-737 along with a reduced uptake of 18F-FDG. Therefore, 18F-FDG uptake could be predictive on sensitivity to treatment with ABT-737. Furthermore, because differentiation treatment of AML cells using ATRA reduced 18F-FDG uptake and increased sensitivity towards ABT-737, a combined treatment regimen with ATRA and ABT-737 might be a promising therapeutic option in the future.

Keywords: 18F-FDG; ABT-737; Cancer metabolism; acute myeloid leukemia; all trans retinoic acid (ATRA); apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biphenyl Compounds
  • Cell Differentiation
  • Fluorodeoxyglucose F18*
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Nitrophenols
  • Piperazines
  • Sulfonamides
  • Tretinoin

Substances

  • ABT-737
  • Biphenyl Compounds
  • Nitrophenols
  • Piperazines
  • Sulfonamides
  • Fluorodeoxyglucose F18
  • Tretinoin