Leukemic B cells clonally identical to myeloma plasma cells are myelomagenic in NOD/SCID mice

被引:56
作者
Pilarski, LM
Seeberger, K
Coupland, RW
Eshpeter, A
Keats, JJ
Taylor, BJ
Belch, AR
机构
[1] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada
[2] Univ Alberta, Dept Oncol, Edmonton, AB T6G 2M7, Canada
关键词
D O I
10.1016/S0301-472X(01)00788-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. In multiple myeloma (MM), the immunoglobulin gene rearrangement characterizing malignant plasma cells is unique. For a patient with multiple myeloma who underwent a B-cell leukemic blast transformation, using the immunoglobulin molecular signature, we characterized the clonal relationship to autologous plasma cells and the impact on normal polyclonal B-lymphocyte populations. Methods. Single-cell reverse transcriptase polymerase chain reaction (RT-PCR)/PCR was used to determine the clonal relationship between autologous MM plasma cells and leukemic B cells. A murine xenograft model was used to determine the myelomagenic potential of the leukemic B cells. Results. Single-cell analysis showed that circulating leukemic-phase cells were clonotypic, with an IgH VDJ sequence identical to that of diagnosis plasma cells. Analysis of IgH transcripts indicates MM clonal dominance over normal B-cell components of the immune system at diagnosis and during leukemic disease. Leukemic B cells were xenografted to irradiated NOD/SCID mice, leading to lytic bone lesions and clonotypic cells in murine BM. Although human cells in murine BM expressed CD138, a marker largely absent from ex vivo leukemic cells, the expression of CD45, CD19, and CD20 confirmed that engrafting cells were mature, probably late-stage B cells rather than plasma cells. Conclusions. Leukemic B cells are able to exert strong clonal dominance over normal components of the immune system, colonize the murine BM in a xenograft model, and disrupt normal bone metabolism leading to lytic bone lesions. This supports the hypothesis that clonotypic MM B cells are reservoirs of disease that persist throughout therapy and give rise to relapse. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.
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页码:221 / 228
页数:8
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