PMID: 9645350Jun 30, 1998Paper

Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

International Journal of Cancer. Journal International Du Cancer
G S SalomonsL A Smets

Abstract

In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies. Frameshift mutations, which result in reduced Bax levels, have also been found in colon cancer of the microsatellite mutator phenotype. Bcl-2 overexpression, or gain of function mutations in the open reading frame (ORF) or in the translational repressor, the upstream ORF(uORF) of bcl-2, might also be important in deregulating its function or expression. We have therefore analyzed 21 bone marrow aspirates from untreated childhood acute lymphoblastic leukaemia and 2 from myeloid leukaemia for mutations in box and bcl-2. DNA sequence analysis of the ORFs of bax and bcl-2 and of the uORF of bcl-2 revealed no mutations, despite the large range in expression levels. Thus, mutations within the (u)ORFs of bax and bcl-2 that (in)activate or deregulate Bax and Bcl-2 are infrequent in primary childhood acute leukaemia and do not play a major role in regulation of the encoded proteins in this disease.

References

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Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·T W SedlakS J Korsmeyer
Jun 11, 1997·International Journal of Cancer. Journal International Du Cancer·G S SalomonsL A Smets

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