Display options
Share it on

J Hematol Oncol. 2016 Sep 22;9(1):95. doi: 10.1186/s13045-016-0324-8.

Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL.

Journal of hematology & oncology

L Fransecky, M Neumann, S Heesch, C Schlee, J Ortiz-Tanchez, S Heller, M Mossner, S Schwartz, L H Mochmann, K Isaakidis, L Bastian, U R Kees, T Herold, K Spiekermann, N Gökbuget, C D Baldus

Affiliations

  1. Department of Hematology and Oncology, Charité, University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany. [email protected].
  2. Department of Hematology and Oncology, Charité, University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
  3. German Cancer Consortium (DKTK), Heidelberg, Germany.
  4. Department of Hematology and Oncology, University Hospital Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
  5. Division of Children´s Leukaemia and Cancer, Telethon Kids Institute, University of Western Australia, Perth, Australia.
  6. Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
  7. Department of Medicine II, Hematology/Oncology, Goethe University Hospital, Frankfurt/Main, Germany.

PMID: 27658391 PMCID: PMC5034449 DOI: 10.1186/s13045-016-0324-8

Abstract

BACKGROUND: GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL).

METHODS: We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL. Of these, we identified 70 of 182 patients with ETP-ALL by immunophenotyping. DNA methylation was assessed genome wide (Illumina Infinium® HumanMethylation450 BeadChip platform) in 12 patients and GATA3-specifically by pyrosequencing in 70 patients with ETP-ALL. The mutational landscape of ETP-ALL with respect to GATA3 expression was investigated in 18 patients and validated by Sanger sequencing in 65 patients with ETP-ALL. Gene expression profiles (Affymetrix Human genome U133 Plus 2.0) of an independent cohort of adult T-ALL (n = 83) were used to identify ETP-ALL and investigate GATA3

RESULTS: In our cohort of 70 ETP-ALL patients, 33 % (23/70) lacked GATA3 expression and were thus defined as GATA3

CONCLUSIONS: We propose GATA3

Keywords: Decitabine; ETP-ALL; GATA3; PER-117

References

  1. Leuk Res. 2007 Apr;31(4):497-506 - PubMed
  2. Leuk Res. 1987;11(5):489-98 - PubMed
  3. Nat Immunol. 2010 Jul;11(7):585-93 - PubMed
  4. Am J Pathol. 2002 Jun;160(6):1945-51 - PubMed
  5. Lancet Oncol. 2009 Feb;10(2):147-56 - PubMed
  6. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  7. Nat Commun. 2016 Apr 06;7:11171 - PubMed
  8. EMBO J. 1991 May;10(5):1187-92 - PubMed
  9. Blood. 2013 Nov 7;122(19):3298-307 - PubMed
  10. J Clin Oncol. 2005 Dec 20;23 (36):9234-42 - PubMed
  11. Immunity. 2011 Aug 26;35(2):299-311 - PubMed
  12. J Histochem Cytochem. 2006 Feb;54(2):161-9 - PubMed
  13. J Clin Oncol. 2010 May 20;28(15):2529-37 - PubMed
  14. Clin Epigenetics. 2013 Feb 01;5(1):3 - PubMed
  15. Immunity. 2012 Nov 16;37(5):813-26 - PubMed
  16. Leuk Res. 2011 Dec;35(12):1585-90 - PubMed
  17. Blood. 2005 Aug 15;106(4):1189-98 - PubMed
  18. Blood Cancer J. 2012 Jan;2(1):e55 - PubMed
  19. Leukemia. 2014 Jan;28(1):1-14 - PubMed
  20. Oncogene. 2010 May 20;29(20):2905-15 - PubMed
  21. Nature. 2008 Apr 10;452(7188):764-7 - PubMed
  22. Nucleic Acids Res. 2009 Jan;37(1):1-13 - PubMed
  23. Blood. 2016 Apr 14;127(15):1863-9 - PubMed
  24. Leuk Res. 2013 Sep;37(9):1027-34 - PubMed
  25. Am J Surg Pathol. 2007 May;31(5):673-80 - PubMed
  26. Oncotarget. 2015 Feb 20;6(5):2754-66 - PubMed
  27. Nat Genet. 2003 Jul;34(3):267-73 - PubMed
  28. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1993-8 - PubMed
  29. Nat Cell Biol. 2013 Feb;15(2):201-13 - PubMed
  30. Nat Genet. 2011 Dec 04;44(1):23-31 - PubMed
  31. Blood. 2010 Nov 18;116(20):4202-11 - PubMed
  32. Nature. 2012 Jan 11;481(7380):157-63 - PubMed
  33. Blood. 2013 Jun 6;121(23):4749-52 - PubMed
  34. PLoS One. 2013;8(1):e53190 - PubMed
  35. PLoS One. 2012;7(6):e38463 - PubMed
  36. J Exp Med. 2009 Dec 21;206(13):2987-3000 - PubMed
  37. Cancer Cell. 2011 Apr 12;19(4):484-97 - PubMed
  38. Cell. 2011 Jan 21;144(2):296-309 - PubMed
  39. Blood Rev. 2011 Mar;25(2):83-90 - PubMed
  40. Nat Genet. 2013 Dec;45(12):1494-8 - PubMed

Publication Types