|
|
Blood, 1 April 2006, Vol. 107, No. 7, pp. 2920-2927.
Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-09-3613.
 Previous Article | Next Article 
Submitted September 8, 2005
Accepted November 15, 2005
Impaired class switch recombination (CSR) in Waldenstrom macroglobulinemia (WM) despite apparently normal CSR machinery
Jitra Kriangkum, Brian J Taylor, Erin Strachan, Michael J Mant, Tony Reiman, Andrew R Belch, and Linda M Pilarski*
Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
* Corresponding author; email: lpilarsk{at}ualberta.ca.
Analysis of clonotypic isotype class switching (CSR) in Waldenstrom macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (MGUS) reveals a normal initial phase of B cell activation as determined by constitutive and inducible expression of activation induced cytidine deaminase (AID). Switch mu (Sµ) analysis shows that large deletions are not common in WM or IgM MGUS. In CD40L/IL-4 stimulated WM cultures from two patients, we observed clonotypic IgG exhibiting intraclonal homogeneity associated with multiple hybrid Sµ/S junctions. This suggests CSR had occurred within WM cells. Nevertheless, the estimated IgG/IgM cell frequency was relatively low (1/1600 cells). Thus, for the majority of WM B cells, CSR does not occur even when stimulated in vitro, suggesting that the WM cell is constitutively unable to or being prevented from carrying out CSR. In contrast to WM, the majority of IgM MGUS clones exhibit intraclonal heterogeneity of IgH V/D/J. Furthermore, most IgM MGUS accumulate more mutations in the upstream Sµ region than do WM, making them unlikely WM progenitors. These observations suggest that switch sequence analysis may identify the subset of patients with IgM MGUS who are at risk of progression to WM.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. J. Taylor, J. Kriangkum, J. A. Pittman, M. J. Mant, T. Reiman, A. R. Belch, and L. M. Pilarski
Analysis of clonotypic switch junctions reveals multiple myeloma originates from a single class switch event with ongoing mutation in the isotype-switched progeny
Blood,
September 1, 2008;
112(5):
1894 - 1903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Martin-Jimenez, R. Garcia-Sanz, A. Balanzategui, M. Alcoceba, E. Ocio, M{a} L. Sanchez, M. Gonzalez, and J. San Miguel
Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstrom's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance
Haematologica,
May 1, 2007;
92(5):
635 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kriangkum, B. J. Taylor, S. P. Treon, M. J. Mant, T. Reiman, A. R. Belch, and L. M. Pilarski
Molecular Characterization of Waldenstrom's Macroglobulinemia Reveals Frequent Occurrence of Two B-Cell Clones Having Distinct IgH VDJ Sequences
Clin. Cancer Res.,
April 1, 2007;
13(7):
2005 - 2013.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Chng, R. F. Schop, T. Price-Troska, I. Ghobrial, N. Kay, D. F. Jelinek, M. A. Gertz, A. Dispenzieri, M. Lacy, R. A. Kyle, et al.
Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma
Blood,
October 15, 2006;
108(8):
2755 - 2763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
