title: 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.
abstract: 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.
authors.affiliation: Department of Molecular Cytogenetics, Blood Transfusion and Hematology Hospital Ho Chi Minh City, Ho Chi Minh City 711512, Vietnam.
authors.forename: Hoang Thanh
authors.initials: HT
authors.lastname: Chi
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108‑8639, Japan.
authors.forename: Bui Thi Kim
authors.initials: BT
authors.lastname: Ly
authors.affiliation: Center for Molecular Biomedicine, The University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 748908, Vietnam.
authors.forename: Hoang Anh
authors.initials: HA
authors.lastname: Vu
authors.affiliation: Japanese Red Cross College of Nursing, Tokyo 150‑0012, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of First Pediatric Hematology, Blood Transfusion and Hematology Hospital Ho Chi Minh City, Ho Chi Minh City 711512, Vietnam.
authors.forename: Phu Chi
authors.initials: PC
authors.lastname: Dung
authors.affiliation: Department of Molecular Cytogenetics, Blood Transfusion and Hematology Hospital Ho Chi Minh City, Ho Chi Minh City 711512, Vietnam.
authors.forename: Phan Thi
authors.initials: PT
authors.lastname: Xinh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D014212:Tretinoin; D051941:fms-Like Tyrosine Kinase 3; D019311:Staurosporine; C059539:midostaurin