02890: Characterizing the LINE-1 Transcriptome in Canine High-grade Peripheral T-cell Lymphoma by RNAseq to Gain Insight into Mechanisms of Drug and Immune Resistance

Grant Status: Open

Grant Amount: $33,234
Paul Hess, DVM, PhD; North Carolina State University
March 1, 2021 - February 28, 2022

Sponsor(s): Golden Retriever FoundationĀ®, Jeffrey Pepper, Westie Foundation of America, Inc.

Breed(s): -All Dogs
Research Program Area: Oncology - Lymphoma
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One Health: Yes

Abstract

High-grade lymphomas are common cancers of white blood cells in dogs. T-cell lymphoma is a particularly aggressive form associated with poor outcomes. Chemotherapy ultimately fails in T-cell lymphoma patients because of a tiny subpopulation of cancer cells – so-called minimal residual disease (MRD) – that resists most drugs, and eventually takes over, leading to short survivals. Researchers will investigate the role of “jumping genes,” a set of genes able to copy and paste themselves into new places in DNA, in T-cell lymphoma. Genes jumping to new spots is disruptive to the integrity of the genetic code, and is permitted only under certain circumstances but can occur when cells become cancerous. Investigators found that jumping genes are unusually active in canine T-cell lymphoma. When cancer cells can suppress jumping gene activity, they can better tolerate chemotherapy drugs and evade immune detection. Researchers hypothesize that MRD emerges during chemotherapy because that subset of cells hijacks a system normally used by reproductive cells to inhibit jumping genes. Investigators plan to use next-generation genetic techniques to define the currently unknown world of active jumping genes in T-cell lymphoma and investigate the molecular causes and consequences of their activity.  A successful study will begin characterizing an unexplored pathway used by lymphoma cells, which could be an important new treatment target in a canine cancer that desperately needs novel therapies.

Publication(s)

None at this time.

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