Molecular medicine reports

Synergistic effect of all‑trans retinoic acid in combination with protein kinase C 412 in FMS-like tyrosine kinase 3-mutated acute myeloid leukemia cells.

PMID 25592076


Acute myeloid leukemia (AML) is a heterogeneous disease. Numerous molecular abnormalities have been identified in AML and, amongst these, FMS‑like tyrosine kinase 3 (FLT3) mutations are one of the most common somatic alterations detected. In the present study, an in vitro investigation was performed to evaluate the effects of all‑trans retinoic acid (ATRA) and PKC412, alone and in combination, in FLT3‑mutated AML cell lines. Trypan blue exclusion test, as well as morphological, western blot and isobologram analyses were conducted. The results indicated that the combined ATRA and PKC412 treatment exhibited additive or synergistic effects in FLT3‑mutated AML cell lines. These results provided in vitro evidence for the future clinical trials evaluating the effects of a combination treatment using PKC412 and ATRA on AML patients with FLT3‑mutations.