Bortezomib mitigates adverse prognosis conferred by Bcl-2 overexpression in patients with relapsed/refractory multiple myeloma

Sikander Ailawadhi, Jeff Miecznikowski, Dan P. Gaile, Dongliang Wang, Taimur Sher, George Mulligan, Barb Bryant, Gregory E. Wilding, Terry Mashtare, Leighton Stein, Aisha Masood, Rachel Neuwirth, Kelvin P. Lee, Asher Chanan-Khan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Overexpression of the Bcl-2 family of genes results in increased transcription of anti-apoptotic proteins. In vitro data suggest that this may enhance acquired chemoresistance and correlate with extramedullary invasion. This has led to pursuing the Bcl-2 family of proteins as therapeutic targets in several malignant disorders, including multiple myeloma (MM). The impact of novel therapeutic agents such as bortezomib on these molecular markers is not known. We investigated the association between the expression of anti-apoptotic members of the Bcl-2 family and the efficacy of bortezomib in patients with relapsed/refractory MM. Gene expression data generated prospectively from large clinical trials were utilized. Hypothesis testing using a multisample test for equivalence was performed. The association between Bcl-2 expression levels and clinical reponse was negated in bortezomib-treated patients (p 0.014), while not so in dexamethasone-treated patients (p 0.92). Similar results were noted for variant 2 of the Mcl-1 gene (p 0.003). Results for Bcl-xl did not meet the level of significance. Thus, the importance of the Bcl-2 family of proteins as prognostic markers in MM should be reassessed in the novel therapeutic agent era. Our data suggest that bortezomib may overcome the prognostic effect conferred by overexpression of some of the anti-apoptotic Bcl-2 family of genes in patients with relapsed/refractory MM.

Original languageEnglish (US)
Pages (from-to)1174-1182
Number of pages9
JournalLeukemia and Lymphoma
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2012

    Fingerprint

Keywords

  • Bcl-2
  • Bortezomib
  • Myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Ailawadhi, S., Miecznikowski, J., Gaile, D. P., Wang, D., Sher, T., Mulligan, G., Bryant, B., Wilding, G. E., Mashtare, T., Stein, L., Masood, A., Neuwirth, R., Lee, K. P., & Chanan-Khan, A. (2012). Bortezomib mitigates adverse prognosis conferred by Bcl-2 overexpression in patients with relapsed/refractory multiple myeloma. Leukemia and Lymphoma, 53(6), 1174-1182. https://doi.org/10.3109/10428194.2011.637212