Molecular basis of targeted therapy in T/NK-cell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

PloS One
Rufino MondejarMiguel A Piris

Abstract

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be ass...Continue Reading

References

Dec 14, 2002·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Forrest D HsuC Blake Gilks
Jul 16, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie VoseUNKNOWN International T-Cell Lymphoma Project
Mar 3, 2010·Annals of Hematology·Ulrike BacherTorsten Haferlach
Sep 3, 2011·Cell Stem Cell·Luisa CimminoIannis Aifantis
May 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Barbara ProAndrei Shustov
Jun 8, 2012·PloS One·Zeynep Kalender AtakStein Aerts
Mar 29, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lina OdqvistMiguel A Piris
Jul 23, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R WillemzeUNKNOWN ESMO Guidelines Working Group
Dec 19, 2013·Blood·Oreofe OdejideDavid M Weinstock
Jan 15, 2014·Nature Genetics·Mamiko Sakata-YanagimotoShigeru Chiba
Feb 6, 2014·Blood·José P VaquéMargarita Sánchez-Beato
Apr 8, 2014·The Oncologist·Javier MunozDavid S Hong
Oct 31, 2014·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Dec 3, 2014·Trends in Biochemical Sciences·Hans KossMatilda Katan
Dec 10, 2014·The Journal of Experimental Medicine·Masao NakagawaLouis M Staudt
Feb 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tzu-Pei ChangIvana Vancurova
Jun 23, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Monique G P van der WijstMarianne G Rots
Jul 21, 2015·Nature Genetics·Jaehyuk ChoiRichard P Lifton
Sep 1, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F d'AmoreUNKNOWN ESMO Guidelines Committee
Oct 6, 2015·Nature Genetics·Keisuke KataokaSeishi Ogawa
Nov 10, 2015·Nature Genetics·Ana Carolina da Silva AlmeidaTeresa Palomero
Dec 30, 2015·Clinical Lymphoma, Myeloma & Leukemia·Salah ArefMohamed Ali El-Baiomy
Jun 9, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alexander M LesokhinJohn Timmerman
Jun 23, 2016·Oncotarget·Lise M LindahlNiels Odum

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Datasets Mentioned

BETA
SUB2029552

Methods Mentioned

BETA
Exome Sequencing
xenograft

Software Mentioned

RUbioSeq
Gene
MiSeq Reporter
Illumina Design Studio
SPSS

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