|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1070-1076
VH Gene Analysis of IgM-Secreting Myeloma
Indicates an Origin From a Memory Cell Undergoing Isotype Switch
Events
Surinder S. Sahota,
Richard Garand,
Razeen Mahroof,
Alastair Smith,
Nadine Juge-Morineau,
Freda K. Stevenson, and
Regis Bataille
From the Molecular Immunology Group, Tenovus Laboratory, and
Department of Haematology, Southampton University Hospitals,
Southampton, UK; and the Laboratoire d'Hematologie, Institut de
Biologie, Centre Hospitalier Universitaire de Nantes, Nantes, France.
IgM-secreting plasma cell tumors are rare variants of typical
isotype-switched multiple myeloma with a similar disease outcome. To
probe the origin and clonal history of these tumors, we have analyzed
VH gene sequences in 6 cases. Potentially functional tumor-derived VH genes were all derived from
VH3, with the V3-7 gene segment being used by 4 of 6. All were somatically mutated, with a mean deviation from germline
sequence of 5.2% (range, 3.1% to 7.1%). The distribution of
replacement mutations was consistent with antigen selection in 4 of 6 cases, and no intraclonal heterogeneity was observed. Clonally related
switched isotype transcripts were sought in 4 cases, and C
transcripts with tumor-derived CDR3 sequence were identified in 2 of 4. These findings indicate that IgM-secreting myelomas are arrested at a
postfollicular stage at which somatic mutation has been silenced.
Isotype switch variants show the cell of origin to be at the IgM to IgG
switch point. These features indicate that the final neoplastic event
has occurred at a stage immediately before that of typical
isotype-switched myeloma. One possibility is that IgM myeloma involves
the previously identified precursor cell of typical myeloma.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Gonzalez, M. van der Burg, R. Garcia-Sanz, J. A. Fenton, A. W. Langerak, M. Gonzalez, J. J. M. van Dongen, J. F. San Miguel, and G. J. Morgan
Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma
Blood,
November 1, 2007;
110(9):
3112 - 3121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kriangkum, B. J. Taylor, S. P. Treon, M. J. Mant, A. R. Belch, and L. M. Pilarski
Clonotypic IgM V/D/J sequence analysis in Waldenstrom macroglobulinemia suggests an unusual B-cell origin and an expansion of polyclonal B cells in peripheral blood
Blood,
October 1, 2004;
104(7):
2134 - 2142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Ellyard, D. T. Avery, T. G. Phan, N. J. Hare, P. D. Hodgkin, and S. G. Tangye
Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow
Blood,
May 15, 2004;
103(10):
3805 - 3812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Avet-Loiseau, R. Garand, L. Lode, J.-L. Harousseau, and R. Bataille
Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants
Blood,
February 15, 2003;
101(4):
1570 - 1571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Sahota, F. Forconi, C. H. Ottensmeier, D. Provan, D. G. Oscier, T. J. Hamblin, and F. K. Stevenson
Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events
Blood,
July 30, 2002;
100(4):
1505 - 1507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhu, H. McCarthy, C. H. Ottensmeier, P. Johnson, T. J. Hamblin, and F. K. Stevenson
Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma
Blood,
April 1, 2002;
99(7):
2562 - 2568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Ottensmeier and F. K. Stevenson
Isotype switch variants reveal clonally related subpopulations in diffuse large B-cell lymphoma
Blood,
October 1, 2000;
96(7):
2550 - 2556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
