Journal article
Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL
Blood, Vol.97(5), pp.1442-1450
03/01/2001
DOI: 10.1182/blood.V97.5.1442
PMID: 11222392
Abstract
Primitive hematopoietic progenitors from some patients with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) express aberrant transcripts for interleukin 3 (IL-3) and granulocyte colony-stimulating factor (G-CSF), and exhibit autonomous proliferation in serum-free cultures that is inhibited by anti–IL-3 and anti–IL-3 receptor antibodies. Expression of the product of the Ph chromosome, the BCR/ABL oncogene, in mice by retroviral bone marrow transduction and transplantation induces CML-like leukemia, and some leukemic mice have increased circulating IL-3, and perhaps granulocyte-macrophage colony-stimulating factor (GM-CSF). These observations raise the possibility of autocrine or paracrine cytokine production in the pathogenesis of human CML. Mice with homozygous inactivation of the Il-3 gene, the Gm-csf gene, or both, were used to test the requirement for these cytokines for induction of CML-like disease by BCR/ABL. Neither IL-3 nor GM-CSF was required in donor, recipient, or both for induction of CML-like leukemia by p210 BCR/ABL. Use of novel mice deficient in both IL-3 and GM-CSF demonstrated that the lack of effect on leukemogenesis was not due to redundancy between these hematopoietic growth factors. Analysis of cytokine levels in leukemic mice where either donor or recipient was Il-3−/−indicated that the increased IL-3 originated from the recipient, suggestive of a host reaction to the disease. These results demonstrate that IL-3 and GM-CSF are not required for BCR/ABL-induced CML-like leukemia in mice and suggest that autocrine production of IL-3 does not play a role in established chronic phase CML in humans.
Details
- Title: Subtitle
- Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL
- Creators
- Shaoguang Li - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MASilke Gillessen - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MAMichael H Tomasson - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MAGlenn Dranoff - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MAD. Gary Gilliland - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MARichard A Van Etten - From The Center for Blood Research, Dana-Farber Cancer Institute, and Harvard Institutes of Medicine and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.97(5), pp.1442-1450
- DOI
- 10.1182/blood.V97.5.1442
- PMID
- 11222392
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 03/01/2001
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094629502771
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