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DC Field | Value | Language |
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dc.citation.endPage | 5077 | - |
dc.citation.number | 25 | - |
dc.citation.startPage | 5068 | - |
dc.citation.title | BLOOD | - |
dc.citation.volume | 121 | - |
dc.contributor.author | Padron, Eric | - |
dc.contributor.author | Painter, Jeffrey S. | - |
dc.contributor.author | Kunigal, Sateesh | - |
dc.contributor.author | Mailloux, Adam W. | - |
dc.contributor.author | McGraw, Kathy | - |
dc.contributor.author | McDaniel, Jessica M. | - |
dc.contributor.author | Kim, Eunhee | - |
dc.contributor.author | Bebbington, Christopher | - |
dc.contributor.author | Baer, Mark | - |
dc.contributor.author | Yarranton, Geoffrey | - |
dc.contributor.author | Lancet, Jeffrey | - |
dc.contributor.author | Komrokji, Rami S. | - |
dc.contributor.author | Abdel-Wahab, Omar | - |
dc.contributor.author | List, Alan F. | - |
dc.contributor.author | Epling-Burnette, Pearlie K. | - |
dc.date.accessioned | 2023-12-22T03:44:36Z | - |
dc.date.available | 2023-12-22T03:44:36Z | - |
dc.date.created | 2016-08-02 | - |
dc.date.issued | 2013-06 | - |
dc.description.abstract | Granulocyte-macrophage-colony-stimulating factor (GM-CSF) hypersensitivity is a hallmark of juvenile myelomonocytic leukemia (JMML) but has not been systematically shown in the related human disease chronic myelomonocytic leukemia (CMML). We find that primary CMML samples demonstrate GM-CSF-dependent hypersensitivity by hematopoietic colony formation assays and phospho-STAT5 (pSTAT5) flow cytometry compared with healthy donors. Among CMML patients, the pSTAT5 hypersensitive response positively correlated with high-risk disease, peripheral leukocytes, monocytes, and signaling-associated mutations. When compared with IL-3 and G-CSF, GM-CSF hypersensitivity was cytokine specific and thus a possible target for intervention in CMML. To explore this possibility, we treated primary CMML cells with KB003, a novel monoclonal anti-GM-CSF antibody, and JAK2 inhibitors. We found that an elevated proportion of immature GM-CSF receptor-a(R) subunit-expressing cells were present in the bone marrow myeloid compartment of CMML. In survival assays, we found that myeloid and monocytic progenitors were sensitive to GM-CSF signal inhibition. Our data indicate that a committed myeloid precursor expressing CD38 may represent the progenitor population with enhanced GM-CSF dependence in CMML, consistent with results in JMML. These preclinical data indicate that GM-CSF signaling inhibitors merit further investigation in CMML and that GM-CSFR expression on myeloid progenitors may be a biomarker for this therapy | - |
dc.identifier.bibliographicCitation | BLOOD, v.121, no.25, pp.5068 - 5077 | - |
dc.identifier.doi | 10.1182/blood-2012-10-460170 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.scopusid | 2-s2.0-84882396666 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/20171 | - |
dc.identifier.url | http://www.bloodjournal.org/content/121/25/5068?sso-checked=true | - |
dc.identifier.wosid | 000321898500016 | - |
dc.language | 영어 | - |
dc.publisher | NW SUITE 200 | - |
dc.title | GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | COLONY-STIMULATING FACTOR | - |
dc.subject.keywordPlus | CYTOKINE RECEPTOR ACTIVATION | - |
dc.subject.keywordPlus | MYELODYSPLASTIC SYNDROMES | - |
dc.subject.keywordPlus | MYELOID-LEUKEMIA | - |
dc.subject.keywordPlus | SCORING SYSTEM | - |
dc.subject.keywordPlus | MYELOPROLIFERATIVE NEOPLASMS | - |
dc.subject.keywordPlus | PROGNOSTIC FACTORS | - |
dc.subject.keywordPlus | SRSF2 MUTATIONS | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | PATHWAY | - |
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