Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

Seelig DM, Ito D, Forster CL, Yoon UA, Breen M, Burns LJ, Bachanova V, Lindblad-Toh K, O'Brien TD, Schmechel SC, Rizzardi AE, Modiano JF, Linden MA

Leuk. Lymphoma 58 (7) 1702-1710 [2017-07-00; online 2016-12-08]

Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

Affiliated researcher

PubMed 27931134

DOI 10.1080/10428194.2016.1260122

Crossref 10.1080/10428194.2016.1260122

pmc: PMC6198319
mid: NIHMS991894

Publications 9.5.0