Publications by authors named "T W McKeithan"

Article Synopsis
  • High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) shares similarities with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), which complicates its diagnosis and treatment.
  • A study on a cohort of 55 patients revealed that about 60% of HGBCL, NOS cases don't express the BL gene signature and instead display characteristics aligned with DLBCL, while showing significant genetic diversity and changes in critical regulatory genes.
  • Pediatric HGBCL, NOS cases exhibited gene expressions typical of GCB-DLBCL and also showed key mutations seen in pediatric BL; the research highlighted PIM1 mutations in adults as a potential target for new therapies.
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Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoma characterized by constitutive NF-κB activation, but whether miR-17∼92 contributes to this activation remains unclear. Herein, we sought to evaluate the role of miR-17∼92 in the process of NF-κB activation in ABC-DLBCL. We found that the expression of miR-17∼92 primary transcript was positively correlated with NF-κB activity, miR-17∼92 activated the NF-κB signaling in ABC-DLBCL, and its over-expression promoted ABC-DLBCL cell growth, accelerated cell G1 to S phase transition and enhanced cell resistance to NF-κB inhibitor.

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Article Synopsis
  • Extra-nodal NK/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive cancer linked to the Epstein-Barr virus, mainly affecting nasal areas.
  • A comprehensive study of 209 ENKTCL cases identified key factors affecting survival, such as disease stage and genetic abnormalities, revealing distinct genetic clusters with different clinical outcomes.
  • The research also highlighted a functional link between specific genetic mutations that promote cell growth, offering insights for potential treatment strategies for this aggressive lymphoma.
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Purpose: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with aggressive clinical behavior. We performed comprehensive miRNA profiling in PTCLs and corresponding normal CD4 Th1/2 and TFH-like polarized subsets to elucidate the role of miRNAs in T-cell lymphomagenesis.

Experimental Design: We used nCounter (NanoString Inc) for miRNA profiling and validated using Taqman qRT-PCR (Applied Biosystems, Inc).

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Extra-nodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive lymphoma, where the tumor suppressor gene (TSG) PRDM1 is frequently lost/inactivated. We employed two different CRISPR/Cas9 approaches to generate PRDM1-/- primary NK cells to study its role in NK-cell homeostasis. PRDM1-/- NK cells showed a marked increase in cloning efficiency, higher proliferation rate and less apoptosis compared with their wild type counterparts.

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