title: Increase of T and B cells and altered BACH2 expression patterns in bone marrow trephines of imatinib-treated patients with chronic myelogenous leukaemia.
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.
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Von Laffert
authors.affiliation: Department of Internal Medicine III, Klinikum Chemnitz gGmbH, D-09113 Chemnitz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
keywords: B and T cell infiltrates/aggregates; BACH2 expression patterns; CD20/BACH2 double-staining; bone marrow trephines; chronic myelogenous leukaemia; imatinib