PMID- 33037771
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20221005
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 24
IP  - 22
DP  - 2020 Nov
TI  - CSF-1R inhibition disrupts the dialog between leukaemia cells and macrophages and 
      delays leukaemia progression.
PG  - 13115-13128
LID - 10.1111/jcmm.15916 [doi]
AB  - Research in the last few years has revealed that leukaemic cells can remodel the 
      bone marrow niche into a permissive environment favouring leukaemic stem cell 
      expansion. Tumour-associated macrophages (TAMs) are prominent components of the 
      tumour microenvironment and play an important role in the onset and progression 
      of solid tumours. However, little is known about their role in the development of 
      acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T-ALL induced 
      by injection of EL4 T-cell lymphoma cells to syngeneic C57BL/6 mice, we report 
      herein that ALL leads to the invasion of leukaemia-associated monocyte-derived 
      cells (LAMs) into the bone marrow and spleen of T-ALL mice. Furthermore, we found 
      that leukaemia cells could polarize bone marrow-derived macrophages (BMDMs) into 
      LAMs. In turn, LAMs were able to protect leukaemia cells from drug-induced 
      apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony 
      stimulating factor-1 receptor (CSF-1R) have emerged as a promising approach for 
      cancer treatment. In this study, we demonstrate that CSF-1R inhibition inhibits 
      the viability of BMDMs, blocks LAMs polarization and reduces the abundance of 
      LAMs in T-ALL mice. In vivo, combination treatment of CSF-1R inhibitor and 
      vincristine (VCR) dramatically increased the survival of T-ALL mice and delayed 
      leukaemia progression compared with VCR monotherapy. Finally, these data 
      reinforce the role of microenvironments in leukaemia and suggest that macrophages 
      are a potential target for the development of novel therapeutic strategies in 
      T-ALL.
CI  - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Li, Kun
AU  - Li K
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Xu, Wenfu
AU  - Xu W
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Lu, Ke
AU  - Lu K
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wen, Yuxi
AU  - Wen Y
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Xin, Tianqing
AU  - Xin T
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Shen, Yaqing
AU  - Shen Y
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Lv, Xueyan
AU  - Lv X
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Hu, Shimin
AU  - Hu S
AD  - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Jin, Runming
AU  - Jin R
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wu, Xiaoyan
AU  - Wu X
AUID- ORCID: 0000-0002-7720-4373
AD  - Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201010
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Csf1r protein, mouse)
RN  - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 5J49Q6B70F (Vincristine)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation, Leukemic
MH  - Leukemia/*metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/*antagonists & 
      inhibitors/*metabolism
MH  - Signal Transduction
MH  - Tumor Microenvironment
MH  - Vincristine/pharmacology
PMC - PMC7701573
OTO - NOTNLM
OT  - CSF-1R
OT  - acute lymphoblastic leukaemia
OT  - tumour-associated macrophage
OT  - vincristine
COIS- None.
EDAT- 2020/10/11 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/11/01
CRDT- 2020/10/10 05:37
PHST- 2020/03/10 00:00 [received]
PHST- 2020/09/03 00:00 [revised]
PHST- 2020/09/05 00:00 [accepted]
PHST- 2020/10/11 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/10/10 05:37 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - JCMM15916 [pii]
AID - 10.1111/jcmm.15916 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2020 Nov;24(22):13115-13128. doi: 10.1111/jcmm.15916. Epub 2020 
      Oct 10.