Home LiteratureArticle Details
PMID: 20160717 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML.

Nature biotechnology ·Vol. 28 ·No. 3 ·2010-03-00 ·Pages 275-80

Saito Y, Uchida N, Tanaka S, Suzuki N, Tomizawa-Murasawa M, Sone A, Najima Y, Takagi S, Aoki Y, Wake A, Taniguchi S, Shultz LD, Ishikawa F

Abstract

Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML). We have previously reported that CD34+CD38- human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rgamma(null) mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.

MeSH Terms
Animals Apoptosis/drug effects Cell Cycle/drug effects Cell Differentiation/drug effects Disease Models, Animal Dose-Response Relationship, Drug Granulocyte Colony-Stimulating Factor/pharmacology Humans Immunohistochemistry Kaplan-Meier Estimate Leukemia, Myeloid, Acute/drug therapy,metabolism,pathology Mice Mice, SCID Neoplastic Stem Cells/drug effects,metabolism,pathology
Chemicals
Granulocyte Colony-Stimulating Factor
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Saito Yoriko
Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
Uchida Naoyuki
Tanaka Satoshi
Suzuki Nahoko
Tomizawa-Murasawa Mariko
Sone Akiko
Najima Yuho
Takagi Shinsuke
Aoki Yuki
Wake Atsushi
Taniguchi Shuichi
Shultz Leonard D
Ishikawa Fumihiko
References (36)
36 references, click to expand
  1. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.
    J Clin Oncol. 2006 Jul 1;24(19):3187-205 PMID: 16682719
  2. Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion.
    Nat Med. 2009 Jun;15(6):696-700 PMID: 19483695
  3. IFNalpha activates dormant haematopoietic stem cells in vivo.
    Nature. 2009 Apr 16;458(7240):904-8 PMID: 19212321
  4. Acute myeloid leukaemia.
    Lancet. 2006 Nov 25;368(9550):1894-907 PMID: 17126723
  5. Stem cell concepts renew cancer research.
    Blood. 2008 Dec 15;112(13):4793-807 PMID: 19064739
  6. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells.
    Cell Stem Cell. 2009 Jul 2;5(1):31-42 PMID: 19570512
  7. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells.
    Cancer Res. 2006 Oct 1;66(19):9339-44 PMID: 16990346
  8. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region.
    Nat Biotechnol. 2007 Nov;25(11):1315-21 PMID: 17952057
  9. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells.
    Cell. 2009 Jul 23;138(2):286-99 PMID: 19632179
  10. Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization.
    Blood. 2009 Aug 13;114(7):1331-9 PMID: 19141863
  11. Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate.
    Clin Cancer Res. 2006 Jan 15;12(2):626-33 PMID: 16428509
  12. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.
    N Engl J Med. 2003 Aug 21;349(8):743-52 PMID: 12930926
  13. A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.
    Blood. 1994 Apr 15;83(8):2086-92 PMID: 7512838
  14. Priming with granulocyte colony-stimulating factor--relation to high-dose cytarabine in acute myeloid leukemia.
    N Engl J Med. 2004 May 20;350(21):2215-6 PMID: 15152074
  15. Cancer stem cells.
    N Engl J Med. 2006 Sep 21;355(12):1253-61 PMID: 16990388
  16. Enhanced chemosensitivity of clonogenic blasts from patients with acute myeloid leukemia by G-CSF, IL-3 or GM-CSF stimulation.
    Leukemia. 1993 Aug;7(8):1191-8 PMID: 7688839
  17. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment.
    Nature. 2005 Jun 16;435(7044):969-73 PMID: 15959517
  18. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.
    Cell. 2008 Dec 12;135(6):1118-29 PMID: 19062086
  19. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial.
    Blood. 2006 Jun 15;107(12):4614-22 PMID: 16484584
  20. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia.
    Nat Med. 2003 Sep;9(9):1158-65 PMID: 12897778
  21. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells.
    Exp Hematol. 2002 Sep;30(9):973-81 PMID: 12225788
  22. Rendering the leukemia cell susceptible to attack.
    N Engl J Med. 2009 Sep 24;361(13):1307-9 PMID: 19776414
  23. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice.
    Blood. 2005 Sep 1;106(5):1565-73 PMID: 15920010
  24. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7 PMID: 9212098
  25. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.
    Blood. 2005 Jul 1;106(1):27-34 PMID: 15761020
  26. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.
    Nature. 1994 Feb 17;367(6464):645-8 PMID: 7509044
  27. The chemokine GRObeta mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment.
    Blood. 2007 Aug 1;110(3):860-9 PMID: 17416737
  28. Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/- all-trans retinoic acid +/- granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome.
    Blood. 1999 Apr 15;93(8):2478-84 PMID: 10194425
  29. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML.
    Blood. 2009 Jun 11;113(24):6215-24 PMID: 18955566
  30. Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9836-41 PMID: 9275212
  31. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100.
    Blood. 2009 Jun 11;113(24):6206-14 PMID: 19050309
  32. Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay.
    Blood. 1997 Jun 1;89(11):3919-24 PMID: 9166828
  33. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches.
    Immunity. 2006 Dec;25(6):977-88 PMID: 17174120
  34. Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells.
    Nature. 2009 Jan 1;457(7225):51-6 PMID: 19122635
  35. Long-term follow-up of allogeneic hematopoietic stem cell transplantation for de novo acute myelogenous leukemia with a conditioning regimen of total body irradiation and granulocyte colony-stimulating factor-combined high-dose cytarabine.
    Biol Blood Marrow Transplant. 2008 Jun;14(6):651-7 PMID: 18489990
  36. Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia.
    Blood. 2004 Jan 15;103(2):489-91 PMID: 12933570
Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.1607
Published
2010-03-00
Epub
2010-00-14
Pages
275-80
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC3857633
Subset
IM
Grants
NCI NIH HHS · R01 CA020408 · United States
NCI NIH HHS · CA20408 · United States
Corrections
CommentIn
PMID: 20212485
CommentIn
PMID: 20362532
External Links
PubMed source DOI: 10.1038/nbt.1607 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2