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Activation-induced ...
Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells
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Feldhahn, Niklas (författare)
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Henke, Nadine (författare)
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Melchior, Kai (författare)
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Duy, Cihangir (författare)
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Soh, Bonaventure Ndikung (författare)
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Klein, Florian (författare)
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von Levetzow, Gregor (författare)
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Giebel, Bernd (författare)
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- Li, Ai-Hong (författare)
- Umeå universitet,Klinisk kemi
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Hofmann, Wolf-Karsten (författare)
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Jumaa, Hassan (författare)
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Müschen, Markus (författare)
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(creator_code:org_t)
- 2007-05-07
- 2007
- Engelska.
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 204:5, s. 1157-1166
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https://umu.diva-por... (primary) (Raw object)
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http://jem.rupress.o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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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.
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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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visa fler...
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von Levetzow, Gr ...
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Giebel, Bernd
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Li, Ai-Hong
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Hofmann, Wolf-Ka ...
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Jumaa, Hassan
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Müschen, Markus
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visa färre...
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Journal of Exper ...
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Umeå universitet