Abstract
In B-cell chronic lymphocytic leukemia (CLL) a high Bcl-2/Bax ratio contributes to death defiance. We sought to identify any genetic changes in the BAX as a possible mechanism for its altered expression in CLL. The BAX gene from the RL cell line and B-cells from 34 CLL patients and 25 controls were sequenced. A novel heterozygous G(-248)A polymorphism in the 5'-UTR was present in 69% of stage I-IV patients and 5.5% of stage 0 patients, and in 4.0% of controls. It was associated with reduced protein expression (P=0.049), progression beyond Rai stage 0 (P=0.00018) and failure to achieve complete response (P=0.038).
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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5' Untranslated Regions / genetics*
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Base Sequence
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Blotting, Western
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Case-Control Studies
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Cyclophosphamide / therapeutic use
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Disease Progression
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Doxorubicin / therapeutic use
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Drug Resistance, Neoplasm / genetics*
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Female
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell / blood
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
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Male
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Middle Aged
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Molecular Sequence Data
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Polymorphism, Single Nucleotide*
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Prednisone / therapeutic use
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2*
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Treatment Outcome
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Vincristine / therapeutic use
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bcl-2-Associated X Protein
Substances
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5' Untranslated Regions
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BAX protein, human
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisone