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Activation-induced ...
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Feldhahn, Niklas
(author)
Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells
- Article/chapterEnglish2007
Publisher, publication year, extent ...
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2007-05-07
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Rockefeller University Press,2007
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-22957
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-22957URI
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https://doi.org/10.1084/jem.20062662DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The Philadelphia chromosome (Ph) encoding the oncogenic BCR-ABL1 kinase defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. ALL cells are derived from B cell precursors in most cases and typically carry rearranged immunoglobulin heavy chain (IGH) variable (V) region genes devoid of somatic mutations. Somatic hypermutation is restricted to mature germinal center B cells and depends on activation-induced cytidine deaminase (AID). Studying AID expression in 108 cases of ALL, we detected AID mRNA in 24 of 28 Ph(+) ALLs as compared with 6 of 80 Ph(-) ALLs. Forced expression of BCR-ABL1 in Ph(-) ALL cells and inhibition of the BCR-ABL1 kinase showed that aberrant expression of AID depends on BCR-ABL1 kinase activity. Consistent with aberrant AID expression in Ph(+) ALL, IGH V region genes and BCL6 were mutated in many Ph(+) but unmutated in most Ph(-) cases. In addition, AID introduced DNA single-strand breaks within the tumor suppressor gene CDKN2B in Ph(+) ALL cells, which was sensitive to BCR-ABL1 kinase inhibition and silencing of AID expression by RNA interference. These findings identify AID as a BCR-ABL1-induced mutator in Ph(+) ALL cells, which may be relevant with respect to the particularly unfavorable prognosis of this leukemia subset.
Added entries (persons, corporate bodies, meetings, titles ...)
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Henke, Nadine
(author)
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Melchior, Kai
(author)
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Duy, Cihangir
(author)
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Soh, Bonaventure Ndikung
(author)
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Klein, Florian
(author)
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von Levetzow, Gregor
(author)
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Giebel, Bernd
(author)
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Li, Ai-HongUmeå universitet,Klinisk kemi(Swepub:umu)liai0001
(author)
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Hofmann, Wolf-Karsten
(author)
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Jumaa, Hassan
(author)
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Müschen, Markus
(author)
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Umeå universitetKlinisk kemi
(creator_code:org_t)
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In:Journal of Experimental Medicine: Rockefeller University Press204:5, s. 1157-11660022-10071540-9538
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Feldhahn, Niklas
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Henke, Nadine
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Melchior, Kai
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Duy, Cihangir
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Soh, Bonaventure ...
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Klein, Florian
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von Levetzow, Gr ...
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