Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

DSpace/Manakin Repository

Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

Citable link to this page

 

 
Title: Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma
Author: Barreca, A; Martinengo, C; Annaratone, L; Righi, L; Chiappella, A; Ladetto, M; Demurtas, A; Chiusa, L; Stacchini, A; Crosetto, N; van Oudenaarden, A; Chiarle, R

Note: Order does not necessarily reflect citation order of authors.

Citation: Barreca, A., C. Martinengo, L. Annaratone, L. Righi, A. Chiappella, M. Ladetto, A. Demurtas, et al. 2014. “Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma.” Blood Cancer Journal 4 (10): e249. doi:10.1038/bcj.2014.67. http://dx.doi.org/10.1038/bcj.2014.67.
Full Text & Related Files:
Abstract: Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients.
Published Version: doi:10.1038/bcj.2014.67
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220646/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454865
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters