PMID- 32374198
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 61
IP  - 8
DP  - 2020 Aug
TI  - Induction of leukemic stem cell differentiation by aryl hydrocarbon receptor 
      agonist and synergy with gilteritinib in FLT3-ITD + acute myeloid leukemia.
PG  - 1932-1942
LID - 10.1080/10428194.2020.1747062 [doi]
AB  - Leukemic stem cells (LSCs) are a major cause of treatment failure and recurrence 
      of acute myeloid leukemia (AML). Targeting LSC is essential to developing a 
      potential cure for patients with relapsed/refractory AML. Here we investigated 
      the effect of aryl hydrocarbon receptor (AhR) signaling on AML stem/progenitor 
      proportion and examined the combined effect of AhR agonist and tyrosine kinase 
      inhibitor. The AhR agonist, 6-formylindolo[3,2-b]carbazole (FICZ), significantly 
      decreased the LSC proportion and clonogenicity and increased differentiation 
      markers in AML primary cells. Synergistic/additive effects of FICZ and 
      gilteritinib, FMS-like tyrosine kinase 3 (FLT3) inhibitor, were confirmed in AML 
      cells with FLT3-ITD. We present evidence that combination of both agents inhibits 
      FLT3 downstream molecules and degrades clonogenicity. Collectively, our results 
      suggest that FICZ not only compels LSC differentiation, but also enhances the 
      efficacy of gilteritinib when combined. Clinical application of this combined 
      approach may pave a new therapeutic strategy for patients with FLT3 mutated AML.
FAU - Han, Heejoo
AU  - Han H
AUID- ORCID: 0000-0001-9907-9131
AD  - Seoul National University College of Medicine, Seoul, Republic of Korea.
AD  - Center for Medical Innovation, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Shin, Dong-Yeop
AU  - Shin DY
AUID- ORCID: 0000-0003-1753-8846
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Kim, Dongchan
AU  - Kim D
AUID- ORCID: 0000-0002-5850-9913
AD  - Seoul National University College of Medicine, Seoul, Republic of Korea.
AD  - Center for Medical Innovation, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Kim, Hyungsuk
AU  - Kim H
AD  - Department of Laboratory Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Lee, Chansup
AU  - Lee C
AD  - Seoul National University College of Medicine, Seoul, Republic of Korea.
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Koh, Youngil
AU  - Koh Y
AUID- ORCID: 0000-0002-8926-8067
AD  - Center for Medical Innovation, Seoul National University Hospital, Seoul, 
      Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Hong, Junshik
AU  - Hong J
AUID- ORCID: 0000-0002-7829-397X
AD  - Seoul National University College of Medicine, Seoul, Republic of Korea.
AD  - Center for Medical Innovation, Seoul National University Hospital, Seoul, 
      Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Yoon, Sung-Soo
AU  - Yoon SS
AD  - Seoul National University College of Medicine, Seoul, Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200506
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Aniline Compounds)
RN  - 0 (Pyrazines)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (gilteritinib)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Aniline Compounds
MH  - Cell Differentiation
MH  - Humans
MH  - *Leukemia, Myeloid, Acute/drug therapy/genetics
MH  - Mutation
MH  - Pyrazines
MH  - Receptors, Aryl Hydrocarbon/genetics
MH  - *fms-Like Tyrosine Kinase 3/genetics
OTO - NOTNLM
OT  - Acute myeloid leukemia
OT  - FMS-like tyrosine kinase 3
OT  - aryl hydrocarbon receptor
OT  - combination treatment
OT  - differentiation
OT  - leukemic stem cell
EDAT- 2020/05/07 06:00
MHDA- 2021/04/28 06:00
CRDT- 2020/05/07 06:00
PHST- 2020/05/07 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/05/07 06:00 [entrez]
AID - 10.1080/10428194.2020.1747062 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2020 Aug;61(8):1932-1942. doi: 10.1080/10428194.2020.1747062. Epub 
      2020 May 6.