PMID- 27817074
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
DP  - 2016 Nov 5
TI  - Potential role of Wnt/beta-catenin signaling in blastic transformation of chronic 
      myeloid leukemia: cross talk between beta-catenin and BCR-ABL.
AB  - Chronic myeloid leukemia (CML) results from malignant transformation of 
      hematopoietic stem cells induced by the BCR-ABL oncogene. Transformation from 
      chronic to blastic phase is the lethal step in CML. Leukemic stem cells (LSCs) 
      are the basic reason for blastic transformation. It has been shown that 
      Wnt/beta-catenin signaling contributes to the self-renewal capacity and 
      proliferation of LSCs in CML. However, the role of Wnt/beta-catenin signaling in 
      blastic transformation of CML is still obscure. Here, we explored the 
      relationship between BCR-ABL and beta-catenin signaling in vitro and in vivo. We 
      found that BCR-ABL stimulated beta-catenin via activation of PI3K/AKT signaling in 
      blastic phase CML cells. Inhibition of the kinase activity of BCR-ABL, PI3K, or 
      AKT decreased the level of beta-catenin in both K562 cells and a CML mouse model and 
      suppressed the transcription of downstream target genes (c-myc and cyclin D1). In 
      addition, inhibition of the BCR-ABL/PI3K/AKT pathway delayed the disease 
      progression in the CML mouse model. To further explore the role of beta-catenin in 
      the self-renewal and survival of CML LSCs, we established a secondary 
      transplantation CML mouse model. Our data revealed that inhibition of the 
      BCR-ABL/PI3K/AKT pathway reduced the tumor-initiating ability of K562 cells, 
      decreased leukemia cell infiltration into peripheral blood and bone marrow, and 
      prolonged the survival of mice. In conclusion, our data indicate a close 
      relationship between beta-catenin and BCR-ABL/PI3K/AKT in blastic phase CML. 
      beta-Catenin inhibition may be of therapeutic value by targeting LSCs in combination 
      with a tyrosine kinase inhibitor, which may delay blastic transformation of CML.
FAU - Hu, Jing
AU  - Hu J
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China.
FAU - Feng, Min
AU  - Feng M
AD  - Institute of Neuroscience, Key Laboratory of Neurobiology, Chongqing Medical 
      University, Chongqing, China.
FAU - Liu, Zhang-Ling
AU  - Liu ZL
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China.
FAU - Huang, Zheng-Lan
AU  - Huang ZL
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China.
FAU - Feng, Wen-Li
AU  - Feng WL
AD  - Department of Clinical Hematology, Key Laboratory of Laboratory Medical 
      Diagnostics Designated by the Ministry of Education, Chongqing Medical 
      University, Chongqing, China. fengwlcqmu@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20161105
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
OTO - NOTNLM
OT  - BCR-ABL
OT  - Blastic transformation
OT  - Chronic myeloid leukemia
OT  - PI3K/AKT
OT  - beta-Catenin
EDAT- 2016/11/07 06:00
MHDA- 2016/11/07 06:00
CRDT- 2016/11/07 06:00
PHST- 2016/05/09 00:00 [received]
PHST- 2016/09/13 00:00 [accepted]
PHST- 2016/11/07 06:00 [entrez]
PHST- 2016/11/07 06:00 [pubmed]
PHST- 2016/11/07 06:00 [medline]
AID - 10.1007/s13277-016-5413-3 [pii]
AID - 10.1007/s13277-016-5413-3 [doi]
PST - aheadofprint
SO  - Tumour Biol. 2016 Nov 5. doi: 10.1007/s13277-016-5413-3.