title: Comparison of BCL-2 and BAX protein expression with in vitro sensitivity to ARA-C and 6TG in AML.
abstract: Activity of BCL-2 protein may be antagonised by BAX protein expression, thereby affecting cellular sensitivity to chemotherapeutic drugs. We analysed the BCL-2 protein expression of blast cells from 19 patients by flow cytometry and immunocytochemistry. This was compared to in vitro sensitivity to the anthracyclines and antimetabolites using the MTT assay. We found a significant correlation between BCL-2 expression and in vitro response to two antimetabolite drugs. One of 7 patients (14%) whose cells were sensitive to ara-C expressed BCL-2 compared to 4/4 patients (100%) whose cells were resistant to ara-C in vitro (p = 0.05). Furthermore, none of the three patients whose cells were sensitive to 6-TG expressed BCL-2 compared to 6/9 patients (67%) whose cells were resistant in vitro (p = 0.045). We found no other correlation between BCL-2 expression and any other chemotherapeutic drug analysed. The ratio of BCL-2 to BAX may be more relevant clinically, therefore cells from a further 9 patients were analysed for both proteins. Whilst there was no overall relationship between BCL-2/BAX ratios and sensitivity to ara-C and 6TG, individual patients could be identified whose blast cells were resistant to ara-C and had high BCL-2/BAX ratios. Further analysis of the significance of these ratios to drug resistance may be of future prognostic value.
authors.affiliation: Pembury Hospital, Kent, United Kingdom.
authors.forename: S E
authors.initials: SE
authors.lastname: Balkham
authors.forename: J M
authors.initials: JM
authors.lastname: Sargent
authors.forename: A W
authors.initials: AW
authors.lastname: Elgie
authors.forename: C J
authors.initials: CJ
authors.lastname: Williamson
authors.forename: C G
authors.initials: CG
authors.lastname: Taylor
mesh_terms: D017209:Apoptosis; D001752:Blast Crisis / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003561:Cytarabine / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013866:Thioguanine / Q000633:toxicity*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003561:Cytarabine; D013866:Thioguanine