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.
authors.affiliation: Division of Hematopoietic Stem Cell and Leukemia Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Yin Wei
authors.initials: YW
authors.lastname: Ho
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Maeda
authors.forename: Allen
authors.initials: A
authors.lastname: Lin
authors.forename: Sung-Uk
authors.initials: SU
authors.lastname: Lee
authors.forename: Alan
authors.initials: A
authors.lastname: Hair
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Claudia
authors.initials: C
authors.lastname: Huettner
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D001549:Benzamides; D002453:Cell Cycle; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics*
chemical_list: D001549:Benzamides; D018925:Chemokines; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl