Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.
In: Nature, Jg. 423 (2003-05-22), Heft 6938, S. 452-456
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Zugriff:
Acute lymphoblastic leukaemia (ALL) is the commonest form of childhood malignancy, and most cases arise from B-cell clones arrested at the pre-B-cell stage of differentiation. The molecular events that arrest pre-B-cell differentiation in the leukaemic pre-B cells have not been well characterized. Here we show that the differentiation regulator SLP-65 (an adaptor protein also called BLNK or BASH) inhibits pre-B-cell leukaemia in mice. Reconstitution of SLP-65 expression in a SLP-65-/- pre-B-cell line led to enhanced differentiation in vitro and prevented the development of pre-B-cell leukaemia in immune-deficient mice. Tyrosine 96 of SLP-65 was required for this activity. The murine SLP-65-/- pre-B-cell leukaemia resembles human childhood pre-B ALL. Indeed, 16 of the 34 childhood pre-B ALL samples that were tested showed a complete loss or drastic reduction of SLP-65 expression. This loss is probably due to the incorporation of alternative exons into SLP-65 transcripts, leading to premature stop codons. Thus, the somatic loss of SLP-65 and the accompanying block in pre-B-cell differentiation might be one of the primary causes of childhood pre-B ALL. [ABSTRACT FROM AUTHOR]
Titel: |
Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.
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Autor/in / Beteiligte Person: | Jumaa, Hassan ; Bossaller, Lukas ; Portugal, Karina ; Storch, Bettina ; Lotz, Michael ; Flemming, Alexandra ; Schrappe, Martin ; Postila, Ville ; Riikonen, Pekka ; Pelkonen, Jukka ; Niemeyer, Charlotte M. ; Reth, Michael |
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Zeitschrift: | Nature, Jg. 423 (2003-05-22), Heft 6938, S. 452-456 |
Veröffentlichung: | 2003 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/nature01608 |
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