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Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation
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Zeitschriftentitel: | Blood |
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Personen und Körperschaften: | , , , , |
In: | Blood, 108, 2006, 6, S. 2006-2012 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society of Hematology
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Schlagwörter: |
Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igμ/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts that reflect reciprocal Igμ/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igμ/BCL6 CT and were not generated from trans-splicing. Both Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Iμ-BCL6 transcripts. The appearance of Igμ/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center–stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.</jats:p> |
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Umfang: | 2006-2012 |
ISSN: |
0006-4971
1528-0020 |
DOI: | 10.1182/blood-2006-03-011536 |