Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia

Bin Zhang; Yin Wei Ho; Qin Huang; Takahiro Maeda; Allen Lin; Sung uk Lee; Alan Hair; Tessa L. Holyoake; Claudia Huettner; Ravi Bhatia

doi:10.1016/j.ccr.2012.02.018

Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia

Bin Zhang, Yin Wei Ho, Qin Huang, Takahiro Maeda, Allen Lin, Sung uk Lee, Alan Hair, Tessa L. Holyoake, Claudia Huettner, Ravi Bhatia

Research output: Contribution to journal › Article › peer-review

277 Citations (Scopus)

Abstract

We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.

Original language	English
Pages (from-to)	577-592
Number of pages	16
Journal	Cancer Cell
Volume	21
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2012.02.018
Publication status	Published - Apr 17 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cell Biology
Cancer Research

UN SDGs

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title = "Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia",

abstract = "We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.",

author = "Bin Zhang and Ho, {Yin Wei} and Qin Huang and Takahiro Maeda and Allen Lin and Lee, {Sung uk} and Alan Hair and Holyoake, {Tessa L.} and Claudia Huettner and Ravi Bhatia",

note = "Funding Information: This work was supported by the National Institutes of Health grants (R01 HL77847 and R01 CA95684 to R.B.) and CR-UK grant (C11074/A11008 to T.H.). We acknowledge the excellent technical support of the COHNMC Analytical Cytometry core, the Clinical Immunobiology Correlative Studies laboratory, and the Animal Resources Center. Procurement of biospecimens was facilitated by the City of Hope Biospecimen Repository Protocol. This study was supported by the Glasgow Experimental Cancer Medicine Centre (ECMC), which is funded by Cancer Research UK and the Chief Scientist's Office (Scotland). ",

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AU - Zhang, Bin

AU - Ho, Yin Wei

AU - Huang, Qin

AU - Maeda, Takahiro

AU - Lin, Allen

AU - Lee, Sung uk

AU - Hair, Alan

AU - Holyoake, Tessa L.

AU - Huettner, Claudia

AU - Bhatia, Ravi

N1 - Funding Information: This work was supported by the National Institutes of Health grants (R01 HL77847 and R01 CA95684 to R.B.) and CR-UK grant (C11074/A11008 to T.H.). We acknowledge the excellent technical support of the COHNMC Analytical Cytometry core, the Clinical Immunobiology Correlative Studies laboratory, and the Animal Resources Center. Procurement of biospecimens was facilitated by the City of Hope Biospecimen Repository Protocol. This study was supported by the Glasgow Experimental Cancer Medicine Centre (ECMC), which is funded by Cancer Research UK and the Chief Scientist's Office (Scotland).

PY - 2012/4/17

Y1 - 2012/4/17

N2 - We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.

AB - We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.

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Altered Microenvironmental Regulation of Leukemic and Normal Stem Cells in Chronic Myelogenous Leukemia

Abstract

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