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Molecular Analysis of Posttransplant Lymphoproliferative Disorders (PTLD) of Donor Origin Occuring in Liver Transplant Patients

Most PTLD occurring in solid organ patients arise from recipient cells, whereas few cases derive from donor transplanted lymphocytes. Donor-derived PTLD usually have a predilection for the allograft and are particularly frequent following liver transplant. To clarify the histogenesis and pathogenesi...

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Bibliographic Details
Published in:Blood 2005-11, Vol.106 (11), p.1916-1916
Main Authors: Capello, Daniela, Muti, Giuliana, Cerri, Michaela, Rossi, Davide, Oreste, Pierluigi, Morra, Enrica, Gaidano, Gianluca
Format: Article
Language:English
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Summary:Most PTLD occurring in solid organ patients arise from recipient cells, whereas few cases derive from donor transplanted lymphocytes. Donor-derived PTLD usually have a predilection for the allograft and are particularly frequent following liver transplant. To clarify the histogenesis and pathogenesis of donor-derived PTLD, we investigated 11 monoclonal PTLD occurring in liver transplant patients, including 6 cases arising from donor cells and 5 cases from recipient cells. Phenotypic markers of histogenesis included expression of BCL6, MUM1 and CD138, which segregate the germinal center (GC) stage of B-cell differentiation (BCL6+/MUM1−/+/CD138−) from later stages of maturation (BCL6−/MUM1+/CD138+/−). Genotypic markers of histogenesis were represented by somatic hypermutation of immunoglobulin variable (IGV) genes, that is experienced by B-cells during GC reaction. To assess the role of antigen in disease pathogenesis, we also analyzed usage and mutational profile of clonal IGV heavy (IGHV) and light (IGLV) chain gene rearrangements. All PTLD or donor origin were EBV-infected lymphoproliferations morphologically classified as polymorphic PTLD (P-PTLD). PTLD arising from recipient cells were classified as diffuse large B-cell lymphomas (DLBCL); EBV infection was restricted to 1 case. Analysis of phenotypic markers of B-cell histogenesis showed expression of the BCL6+/MUM1−/CD138− profile in 3 DLBCL with centroblastic features, all arising from recipient cells. The phenotypic profile BCL-6−/MUM1+/CD138+/−, consistent with a post-GC stage of pre-terminal B-cell differentiation, was detected in 8/11 PTLD, including 6/6 donor-derived PTLD and 2/5 recipient-derived PTLD. Analysis of somatic hypermutation showed the presence of somatically hypermutated IGHV genes in 7/11 PTLD. Unmutated IGHV rearrangements were identified in 2/6 donor-derived PTLD and in 2/5 recipient-derived PTLD. Analysis of intraclonal heterogeneity showed the presence of ongoing mutations in 1 donor-derived PTLD. The distribution of individual IGHV families and genes differed between donor-derived and recipient-derived PTLD and between the normal repertoire and donor-derived PTLD. Donor-derived PTLD preferentially rearranged IGHV3 (2/6 cases) and IGHV4 (3/6 cases) family genes, whereas recipient-derived PTLD rearranged virtually all IGVH families. The IGHV4-39 gene was the most frequently rearranged IGHV gene in donor-derived PTLD (3/6 cases), but was absent in recipient-derived PTLD and relati
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V106.11.1916.1916