Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures

Abstract

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct ''tumor profile signatures'' for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, a-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

“…In particular, BCL2A1 developmentally regulated in B and T cells, where it sustains the viability of T lymphoblasts (26,38). In cancer cell lines, BCL2A1 is overexpressed in certain human epithelial and hematopoietic malignancies such as diffuse large B cell lymphoma and B cell chronic lymphocytic leukemia (39,40). Using multiple approaches to inactivate ALK signaling in ALCL cells, we demonstrated that BCL2A1 is a specific NPM-ALK-regulated gene.…”

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

“…Syk has been suggested as a potential therapeutic target for PTCL by Mahadevan et al, 19 but previous data on Syk expression in T-cell lymphomas are limited and somewhat conflicting. A small study found Syk in only 2/19 PTCLs by IHC, including 1/8 PTCL-U and 1/1 mycosis fungoid (weak staining).…”

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors

“…The GIST-R (0.5 mM IM) cell line was treated with MP470 (1 mM) for 6 and 24 h. Total RNA was extracted from GIST-S, GIST-R (0.5 mM IM) and MP470-treated GIST-R at 6 and 24 h utilizing the RNeasy Mini Kit (Qiagen, CA, USA) as described previously (Mahadevan et al, 2005b). …”