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Article: Central role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia

TitleCentral role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia
Authors
Issue Date1992
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH
Citation
British Journal Of Haematology, 1992, v. 80 n. 1, p. 40-48 How to Cite?
AbstractIn previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-α Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-α Ab and anti-granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM-CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF-α produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-α effect. Expression studies of TNF-α and TNF-α receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-α activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-α values. Recombinant interleukin-1 alpha (IL-1α) also stimulated JCML, colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-α or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-α and that the endogenously-produced TNF-α and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1α also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF-α or both.
Persistent Identifierhttp://hdl.handle.net/10722/170254
ISSN
2015 Impact Factor: 5.401
2015 SCImago Journal Rankings: 2.313
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFreedman, MHen_US
dc.contributor.authorCohen, Aen_US
dc.contributor.authorGrunberger, Ten_US
dc.contributor.authorBunin, Nen_US
dc.contributor.authorLuddy, REen_US
dc.contributor.authorSaunders, EFen_US
dc.contributor.authorShahidi, Nen_US
dc.contributor.authorLau, Aen_US
dc.contributor.authorEstrov, Zen_US
dc.date.accessioned2012-10-30T06:07:00Z-
dc.date.available2012-10-30T06:07:00Z-
dc.date.issued1992en_US
dc.identifier.citationBritish Journal Of Haematology, 1992, v. 80 n. 1, p. 40-48en_US
dc.identifier.issn0007-1048en_US
dc.identifier.urihttp://hdl.handle.net/10722/170254-
dc.description.abstractIn previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-α Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-α Ab and anti-granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM-CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF-α produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-α effect. Expression studies of TNF-α and TNF-α receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-α activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-α values. Recombinant interleukin-1 alpha (IL-1α) also stimulated JCML, colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-α or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-α and that the endogenously-produced TNF-α and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1α also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF-α or both.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJHen_US
dc.relation.ispartofBritish Journal of Haematologyen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBone Marrow - Immunologyen_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshColony-Forming Units Assayen_US
dc.subject.meshFemaleen_US
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor - Immunologyen_US
dc.subject.meshHematopoiesis - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInfanten_US
dc.subject.meshInterleukin-1 - Immunologyen_US
dc.subject.meshLeukemia, Myelogenous, Chronic, Bcr-Abl Positive - Genetics - Immunologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshReceptors, Cell Surface - Geneticsen_US
dc.subject.meshReceptors, Tumor Necrosis Factoren_US
dc.subject.meshRecombinant Proteins - Immunologyen_US
dc.subject.meshTumor Cells, Cultured - Immunologyen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Immunologyen_US
dc.titleCentral role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemiaen_US
dc.typeArticleen_US
dc.identifier.emailLau, A:asylau@hku.hken_US
dc.identifier.authorityLau, A=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1365-2141.1992.tb06398.x-
dc.identifier.pmid1311195-
dc.identifier.scopuseid_2-s2.0-0026533915en_US
dc.identifier.volume80en_US
dc.identifier.issue1en_US
dc.identifier.spage40en_US
dc.identifier.epage48en_US
dc.identifier.isiWOS:A1992HC13000007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridFreedman, MH=7203068454en_US
dc.identifier.scopusauthoridCohen, A=7404782058en_US
dc.identifier.scopusauthoridGrunberger, T=7004211895en_US
dc.identifier.scopusauthoridBunin, N=7003608320en_US
dc.identifier.scopusauthoridLuddy, RE=6603961711en_US
dc.identifier.scopusauthoridSaunders, EF=7102174409en_US
dc.identifier.scopusauthoridShahidi, N=36839446400en_US
dc.identifier.scopusauthoridLau, A=7202626202en_US
dc.identifier.scopusauthoridEstrov, Z=7005487081en_US

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