Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo

V. Cull; P.A Tilbrook; A.S Adenan; D. Chappell; E. Ingley; M.K Sarna; T N. Palmer; S.S Watowich; S.P. Klinken

doi:10.1038/sj.onc.1203370

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Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo

Journal article

Peer reviewed

Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo

V. Cull, P.A Tilbrook, A.S Adenan, D. Chappell, E. Ingley, M.K Sarna, T N. Palmer, S.S Watowich and S.P. Klinken

Oncogene, Vol.19(7), pp.953-960

2000

DOI: https://doi.org/10.1038/sj.onc.1203370

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Abstract

J2E cells produce rapid, fatal erythroleukemias in vivo but still respond to erythropoietin (epo) in vitro by differentiating, proliferating and remaining viable in the absence of serum. Mutant epo receptors were introduced into these cells to determine whether they could influence the different biological responses to epo in vitro and the development of erythroleukemias. Three mutant receptors were used as cytoplasmic truncation mutants Delta257 and Delta321 (above box 1 and below box 2 respectively), and the cytoplasmic point mutant W282R (defective for JAK2 activation). Strikingly, the Delta321 mutation produced a hyper-sensitive response in vitro to epo-induced differentiation and viability, but not to proliferation. In contrast with the Delta321 receptor, the Delta257 and W282R mutants inhibited all biological responses to epo due to impaired JAK2 phosphorylation. Significantly, erythroleukemias took almost twice as long to develop with cells containing the W282R mutation, indicating that JAK2 plays an important role in the emergence of these leukemias. These data demonstrate that mutant epo receptors dominantly altered responses of J2E cells to epo in culture and the development of erythroleukemias. Oncogene (2000) 19, 953 - 960.

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Title: Dominant action of mutated erythropoietin receptors on differentiation in vitro and erythroleukemia development in vivo
Authors/Creators: V. Cull (Author/Creator) - The University of Western Australia
P.A Tilbrook (Author/Creator) - The University of Western Australia
A.S Adenan (Author/Creator) - The University of Western Australia
D. Chappell (Author/Creator) - The University of Western Australia
E. Ingley (Author/Creator) - The University of Western Australia
M.K Sarna (Author/Creator) - The University of Western Australia
T N. Palmer (Author/Creator) - The University of Western Australia
S.S Watowich (Author/Creator) - Institute of Immunology
S.P. Klinken (Author/Creator) - The University of Western Australia
Publication Details: Oncogene, Vol.19(7), pp.953-960
Publisher: Nature Publishing Group
Identifiers: 991005542603107891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.184 Physiology & Metals; 1.184.1030 Erythropoietin Therapy
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Oncology
ESI research areas: Molecular Biology & Genetics