PMID- 30595549
OWN - NLM
STAT- MEDLINE
DCOM- 20200227
LR  - 20200309
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 12
IP  - 1
DP  - 2019 Jan 8
TI  - Hif-1alpha Deletion May Lead to Adverse Treatment Effect in a Mouse Model 
      of MLL-AF9-Driven AML.
PG  - 112-121
LID - S2213-6711(18)30492-2 [pii]
LID - 10.1016/j.stemcr.2018.11.023 [doi]
AB  - Relapse of acute myeloid leukemia (AML) remains a significant clinical challenge 
      due to limited therapeutic options and poor prognosis. Leukemic stem cells (LSCs) 
      are the cellular units responsible for relapse in AML, and strategies that target 
      LSCs are thus critical. One proposed potential strategy to this end is to break 
      the quiescent state of LSCs, thereby sensitizing LSCs to conventional 
      cytostatics. The hypoxia-inducible factor (HIF) pathway is a main driver of 
      cellular quiescence and a potential therapeutic target, with precedence from both 
      solid cancers and leukemias. Here, we used a conditional knockout Hif-1alpha mouse 
      model together with a standard chemotherapy regimen to evaluate LSC targeting in 
      AML. Contrary to expectation, our studies revealed that Hif-1alpha-deleted-leukemias 
      displayed a faster disease progression after chemotherapy. Our studies thereby 
      challenge the general notion of cancer stem cell sensitization by inhibition of 
      the HIF pathway, and warrant caution when applying HIF inhibition in combination 
      with chemotherapy in AML.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Velasco-Hernandez, Talia
AU  - Velasco-Hernandez T
AD  - Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC 
      B12, Solvegatan 17, 22184 Lund, Sweden. Electronic address: 
      tvelasco@carrerasresearch.org.
FAU - Soneji, Shamit
AU  - Soneji S
AD  - Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC 
      B12, Solvegatan 17, 22184 Lund, Sweden.
FAU - Hidalgo, Isabel
AU  - Hidalgo I
AD  - Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC 
      B12, Solvegatan 17, 22184 Lund, Sweden.
FAU - Erlandsson, Eva
AU  - Erlandsson E
AD  - Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC 
      B12, Solvegatan 17, 22184 Lund, Sweden.
FAU - Cammenga, Jorg
AU  - Cammenga J
AD  - Department of Hematology, Linkoping University Hospital, 58183 Linkoping, Sweden; 
      Department of Clinical and Experimental Medicine, Linkoping University, 58183 
      Linkoping, Sweden.
FAU - Bryder, David
AU  - Bryder D
AD  - Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC 
      B12, Solvegatan 17, 22184 Lund, Sweden; Sahlgrenska Cancer Center, Gothenburg 
      University, 40530 Gothenburg, Sweden. Electronic address: david.bryder@med.lu.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181227
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (MLL-AF9 fusion protein, mouse)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*adverse effects/therapeutic use
MH  - Gene Deletion
MH  - Hypoxia-Inducible Factor 1/*genetics/metabolism
MH  - Leukemia, Myeloid, Acute/drug therapy/*genetics
MH  - Mice
MH  - Myeloid Progenitor Cells/cytology/metabolism
MH  - Oncogene Proteins, Fusion/genetics
MH  - Protein Interaction Maps
MH  - Single-Cell Analysis
PMC - PMC6335588
OTO - NOTNLM
OT  - HIF-1alpha
OT  - acute myeloid leukemia
OT  - chemotherapy
OT  - hypoxia
OT  - mouse model
OT  - single-cell transcriptional analysis
EDAT- 2019/01/01 06:00
MHDA- 2020/02/28 06:00
PMCR- 2018/12/27
CRDT- 2019/01/01 06:00
PHST- 2018/09/11 00:00 [received]
PHST- 2018/11/30 00:00 [revised]
PHST- 2018/11/30 00:00 [accepted]
PHST- 2019/01/01 06:00 [pubmed]
PHST- 2020/02/28 06:00 [medline]
PHST- 2019/01/01 06:00 [entrez]
PHST- 2018/12/27 00:00 [pmc-release]
AID - S2213-6711(18)30492-2 [pii]
AID - 10.1016/j.stemcr.2018.11.023 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2019 Jan 8;12(1):112-121. doi: 10.1016/j.stemcr.2018.11.023. 
      Epub 2018 Dec 27.