11:22 AM
Apr 13, 2018
 |  BC Extra  |  Preclinical News

NCI identifies new lymphoma subtypes

A New England Journal of Medicine paper out of NIH's National Cancer Institute revealed new subtypes of diffuse large B cell lymphomas (DLBCL) that could lead to more targeted therapeutic strategies. The report adds to a growing body of literature that supports classifying and treating tumors based on tumor biology rather than the tissue type from which the tumor arose.

The study sought to refine established DLBCL subtypes into subtypes based on genetic and expression profiles. Current DLBCL subgroups -- activated B-cell-like (ABC) and germinal-center B-cell-like (GCB) -- were classified according to cells of origin. The authors noted that the ABC and GCB classifications did not account for all types of DLBCL or accurately predict responses to drugs such as Imbruvica ibrutinib, a Bruton's tyrosine kinase (Btk) inhibitor marketed by AbbVie Inc. (NYSE:ABBV).

The group used genomic analyses of 574 biopsy samples from patients with DLBCL to identify four new subtypes of the disease based on mutation status: MCD, N1, BN2 and EZB. When matched with clinical data, N1 and MCD had significantly worse probabilities of progression-free and overall survival compared with EZB and BN2 subtypes. The study predicted five-year OS rates of 26% for MCD, 36% for N1, 65% for BN2 and 68% for EZB.

By comparing gene expression among subtypes, the researchers found mutations in negative regulators of proximal B cell receptor signaling were most frequent in MCD cancer types, including alterations in CD79 molecule immunoglobulin-associated alpha (CD79A) and beta (CD79B), and least frequent in EZB. BN2 cancer types were enriched for mutations in regulators of I-kappa B kinase (IKK) or the B cell receptor-NF-kB signaling axis.

The authors suggest these and other subtype-specific gene expression analyses could better identify targets to tailor therapies for DLBCL patients than existing ABC and GCB classifications.

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