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Oncol Lett. 2016 Oct;12(4):2421-2428. doi: 10.3892/ol.2016.4964. Epub 2016 Aug 05.

Increase of T and B cells and altered BACH2 expression patterns in bone marrow trephines of imatinib-treated patients with chronic myelogenous leukaemia.

Oncology letters

Maximilian Von Laffert, Mathias Hänel, Manfred Dietel, Ioannis Anagnostopoulos, Korinna Jöhrens

Affiliations

  1. Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
  2. Department of Internal Medicine III, Klinikum Chemnitz gGmbH, D-09113 Chemnitz, Germany.

PMID: 27698808 PMCID: PMC5038374 DOI: 10.3892/ol.2016.4964

Abstract

The effect of imatinib on T and B cells in patients with chronic myelogenous leukaemia (CML) is not well understood. An upregulation of the transcription factor Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar 1 bZip transcription factor 2 (BACH2), which is involved in the development and differentiation of B cells, was demonstrated in a CML cell line treated with imatinib. The present study retrospectively analysed the expression and distribution of cluster of differentiation (CD)3, CD20 and BACH2 (per 1,000 cells), as well as the co-expression of CD20 and BACH2, using immunohistochemistry in serial bone marrow trephines obtained from 14 CML patients treated with imatinib in comparison to 17 patients with newly diagnosed CML and 6 control trephines. Bone marrow trephines of CML patients in remission under imatinib therapy exhibited significantly higher numbers of CD3 and CD20 infiltrates (partly ordered in aggregates) compared with patients with newly diagnosed CML and control individuals. Similarly, nuclear expression of BACH2 in granulopoietic cells was increased in CML patients treated with imatinib, which may represent the histological correlate of the positive treatment effect. Furthermore, since BACH2 is involved in B cell development, its altered expression patterns by imatinib may be one explanation for high B cell numbers, as revealed by CD20/BACH2 (nuclear)-positive cells. As the present data are preliminary, future prospective studies are required to assess the prognostic and predictive role of BACH2 in patients with CML under targeted therapy.

Keywords: B and T cell infiltrates/aggregates; BACH2 expression patterns; CD20/BACH2 double-staining; bone marrow trephines; chronic myelogenous leukaemia; imatinib

References

  1. Genes Chromosomes Cancer. 2007 Jan;46(1):67-74 - PubMed
  2. Eur J Haematol. 2010 Nov;85(5):387-98 - PubMed
  3. Mol Cell Biol. 1996 Nov;16(11):6083-95 - PubMed
  4. Int J Oncol. 2007 Nov;31(5):1133-9 - PubMed
  5. Exp Hematol. 2007 Aug;35(8):1266-71 - PubMed
  6. Blood. 2010 Aug 5;116(5):772-82 - PubMed
  7. J Natl Cancer Inst. 2011 Apr 6;103(7):553-61 - PubMed
  8. Cancer Immunol Immunother. 2007 Jun;56(6):849-61 - PubMed
  9. Blood. 2006 Nov 15;108(10):3406-13 - PubMed
  10. EMBO J. 1998 Oct 1;17(19):5734-43 - PubMed
  11. EMBO J. 2010 Dec 1;29(23):3896-7 - PubMed
  12. Semin Immunol. 2011 Oct;23(5):341-9 - PubMed
  13. J Clin Oncol. 2005 Nov 1;23(31):8012-7 - PubMed
  14. N Engl J Med. 2001 Apr 5;344(14):1031-7 - PubMed
  15. Blood. 2007 Feb 1;109 (3):1211-9 - PubMed
  16. J Clin Invest. 2000 Jan;105(1):3-7 - PubMed
  17. PLoS One. 2011 Apr 18;6(4):e18925 - PubMed
  18. Protein Cell. 2010 Feb;1(2):124-32 - PubMed
  19. Acta Crystallogr D Biol Crystallogr. 2012 Jan;68(Pt 1):26-34 - PubMed
  20. N Engl J Med. 2001 Apr 5;344(14):1038-42 - PubMed
  21. PLoS One. 2013 Aug 02;8(8):e69126 - PubMed
  22. Blood. 2010 Feb 25;115(8):1512-8 - PubMed
  23. J Biochem. 2007 Jun;141(6):783-9 - PubMed
  24. Am J Hematol. 2011 Apr;86(4):346-50 - PubMed
  25. Genes Chromosomes Cancer. 2001 Dec;32(4):353-63 - PubMed
  26. Am J Hematol. 2012 Nov;87(11):1037-45 - PubMed
  27. Genes Cancer. 2012 May;3(5-6):447-54 - PubMed
  28. Blood. 2004 Jan 15;103(2):538-44 - PubMed
  29. Blood. 2003 Nov 1;102(9):3317-22 - PubMed
  30. Blood. 2014 Feb 13;123(7):950 - PubMed
  31. Blood. 2005 Mar 15;105(6):2473-9 - PubMed
  32. Blood. 2004 Aug 15;104(4):1094-9 - PubMed
  33. Clin Cancer Res. 2005 Mar 1;11(5):1928-40 - PubMed

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