Premium
Mcl‐1 and Bcl‐2/Bax ratio are associated with treatment response but not with Rai stage in B‐cell chronic lymphocytic leukemia
Author(s) -
Saxena Anurag,
Viswanathan Sathiyanarayanan,
Moshynska Oksana,
Tandon Puneeta,
Sankaran Koravangattu,
Sheridan David P.
Publication year - 2004
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10453
Subject(s) - chronic lymphocytic leukemia , chlorambucil , prednisone , medicine , stage (stratigraphy) , gastroenterology , apoptosis , complete response , bcl 2 associated x protein , blot , leukemia , immunology , chemotherapy , chemistry , biology , caspase 3 , programmed cell death , cyclophosphamide , gene , biochemistry , paleontology
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. Am. J. Hematol. 75:22–33, 2004. © 2003 Wiley‐Liss, Inc.