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Mcl-1 and Bcl-2/Bax ratio are associated with treatment response but not with Rai stage in B-cell chronic lymphocytic leukemia.
- Source :
-
American journal of hematology [Am J Hematol] 2004 Jan; Vol. 75 (1), pp. 22-33. - Publication Year :
- 2004
-
Abstract
- Although both Bcl-2/Bax ratio and Mcl-1 have been identified to be of clinical relevance in B-cell chronic lymphocytic leukemia (CLL), there is controversy regarding their role; further, their relative importance is not well delineated. Expression of Bcl-2, Bax, the Bcl-2/Bax ratio, and Mcl-1 in 51 consecutive previously untreated CLL patients and 16 controls was determined by Western blotting. Only 37 patients were treated, all with chlorambucil and prednisone initially. Six patients achieved complete response (CR), 14 were non-responders (NR), and 17 had a partial response (PR), as defined by NCI criteria. There was considerable inter-patient variability in protein expression and overlap with healthy volunteers (P > 0.05). All patients with CR had low Mcl-1 levels compared to the PR + NR group (0.07 +/- 0.02 vs. 0.14 +/- 0.07, P = 0.043). Higher Mcl-1 expression as determined by dichotomizing the data was associated with a failure to achieve CR (P = 0.021). The Bcl-2/Bax ratio was significantly associated with treatment response only when CR and PR were considered together (0.89 +/- 0.53 [CR + PR] vs. 3.38 +/- 4.47 [NR], P = 0.0118). There was no association with Rai stage. Low Mcl-1 appears to be a requirement for CR, while low Bcl-2/Bax ratio is indicative of some response to conventional treatment.<br /> (Copyright 2003 Wiley-Liss, Inc.)
- Subjects :
- Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating therapeutic use
Antineoplastic Agents, Hormonal therapeutic use
Chlorambucil therapeutic use
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Male
Middle Aged
Myeloid Cell Leukemia Sequence 1 Protein
Neoplasm Staging
Prednisone therapeutic use
ROC Curve
Treatment Outcome
bcl-2-Associated X Protein
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell metabolism
Neoplasm Proteins metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0361-8609
- Volume :
- 75
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 14695629
- Full Text :
- https://doi.org/10.1002/ajh.10453