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

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.

journal_name

Int J Cancer

authors

Salomons GS,Buitenhuis CK,Martínez Muñoz C,Verwijs-Jassen M,Behrendt H,Zsiros J,Smets LA

doi

10.1002/(sici)1097-0215(19980619)79:3<273::aid-ijc

subject

Has Abstract

pub_date

1998-06-19 00:00:00

pages

273-7

issue

3

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19980619)79:3<273::AID-IJC

journal_volume

79

pub_type

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