Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target

Yang Yang; Saradhi Mallampati; Baohua Sun; Jing Zhang; Sang Bae Kim; Ju Seog Lee; Yun Gong; Zhen Cai; Xiaoping Sun

doi:10.1016/j.canlet.2012.11.056

Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target

Yang Yang, Saradhi Mallampati, Baohua Sun, Jing Zhang, Sang Bae Kim, Ju Seog Lee, Yun Gong, Zhen Cai, Xiaoping Sun

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66 Scopus citations

Abstract

Leukemia cells are protected by various components of their microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.

Original language	English (US)
Pages (from-to)	9-17
Number of pages	9
Journal	Cancer Letters
Volume	333
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2012.11.056
State	Published - Jun 1 2013

Keywords

Acute lymphoblastic leukemia
Bone marrow stromal cells
Chemotherapy resistance
Wnt pathway
Wnt pathway inhibitor

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility
Functional Proteomics Reverse Phase Protein Array Core
Research Animal Support Facility
Clinical Trials Office

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10.1016/j.canlet.2012.11.056

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title = "Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target",

abstract = "Leukemia cells are protected by various components of their microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.",

keywords = "Acute lymphoblastic leukemia, Bone marrow stromal cells, Chemotherapy resistance, Wnt pathway, Wnt pathway inhibitor",

author = "Yang Yang and Saradhi Mallampati and Baohua Sun and Jing Zhang and Kim, {Sang Bae} and Lee, {Ju Seog} and Yun Gong and Zhen Cai and Xiaoping Sun",

note = "Funding Information: We thank Dr. J. G. Wen at Methodist Hospital, Houston, Texas, USA, for the human bone marrow MSC cell line HS; Dr. Patrick Zweidler-McKay at MD Anderson for the human leukemia cell lines Reh, RS4;11, and SEMK2, Dr. Jan Burger at MD Anderson for the murine MSC line M2-10B4, and Dr. Roel Nusse at Stanford University for 7TGC reporter vector (obtained from Addgene; plasmid-24304). This work was supported in part by Research Scholar Grant 119645-RSG-10-131-01-DDC to X.S. from the American Cancer Society, a Physician Scientist Program Award to X.S. from MD Anderson, a scholarship award and National Natural Science Foundation of China (no. 81200385) to Y.Y. from the China Scholarship Council, an award to Z.C. from the High Level Health Technology Innovation of Elite Culture Program of Zhejiang Province, and the MD Anderson Support Grant CA016672. ",

year = "2013",

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doi = "10.1016/j.canlet.2012.11.056",

language = "English (US)",

volume = "333",

pages = "9--17",

journal = "Cancer Letters",

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T1 - Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target

AU - Yang, Yang

AU - Mallampati, Saradhi

AU - Sun, Baohua

AU - Zhang, Jing

AU - Kim, Sang Bae

AU - Lee, Ju Seog

AU - Gong, Yun

AU - Cai, Zhen

AU - Sun, Xiaoping

N1 - Funding Information: We thank Dr. J. G. Wen at Methodist Hospital, Houston, Texas, USA, for the human bone marrow MSC cell line HS; Dr. Patrick Zweidler-McKay at MD Anderson for the human leukemia cell lines Reh, RS4;11, and SEMK2, Dr. Jan Burger at MD Anderson for the murine MSC line M2-10B4, and Dr. Roel Nusse at Stanford University for 7TGC reporter vector (obtained from Addgene; plasmid-24304). This work was supported in part by Research Scholar Grant 119645-RSG-10-131-01-DDC to X.S. from the American Cancer Society, a Physician Scientist Program Award to X.S. from MD Anderson, a scholarship award and National Natural Science Foundation of China (no. 81200385) to Y.Y. from the China Scholarship Council, an award to Z.C. from the High Level Health Technology Innovation of Elite Culture Program of Zhejiang Province, and the MD Anderson Support Grant CA016672.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Leukemia cells are protected by various components of their microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.

AB - Leukemia cells are protected by various components of their microenvironment, including marrow stromal cells (MSCs). To understand the molecular mechanisms underlying this protection, we cultured acute lymphoblastic leukemia (ALL) cells with MSCs and studied the effect of the latter on the molecular profiling of ALL cells at the mRNA and protein levels. Our results indicated that activated Wnt signaling in ALL cells is involved in MSC-mediated drug resistance. Blocking the Wnt pathway sensitized the leukemia cells to chemotherapy and improved overall survival in a mouse model. Targeting the Wnt pathway may be an innovative approach to the treatment of ALL.

KW - Acute lymphoblastic leukemia

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KW - Wnt pathway inhibitor

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Wnt pathway contributes to the protection by bone marrow stromal cells of acute lymphoblastic leukemia cells and is a potential therapeutic target

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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