title: Association of a novel single nucleotide polymorphism, G(-248)A, in the 5'-UTR of BAX gene in chronic lymphocytic leukemia with disease progression and treatment resistance.
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).
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein
chemical_list: D020121:5' Untranslated Regions; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone