|
|
Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-05-1585.
Submitted May 16, 2003
Accepted June 22, 2003
Activation induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone
Emilia Albesiano, Bradley T Messmer, Rajendra N Damle, Steven L Allen, Kanti R Rai, and Nicholas Chiorazzi*
Department of Experimental Immunology, North Shore-LIJ Research Institute, Manhasset, NY, USA; Department of Medicine, North Shore University Hospital and NYU School of Medicine, Manhasset, NY, USA
Department of Medicine, Long Island Jewish Medical Center and Albert Einstein College, New Hyde Park, NY, USA
* Corresponding author; email: nchizzi{at}nshs.edu.
The degree of somatic mutation of immunoglobulin variable (Ig V) region genes is an important prognostic indicator of clinical course and outcome in B-CLL, although the reason for this association remains unclear. Furthermore, some B-CLL cells continue to acquire Ig V gene mutations after the transforming event. Since activation-induced cytidine deaminase (AID) is an essential component of the canonical somatic hypermutation process in normal B cells, its expression in B-CLL is potentially relevant to the disease. We detected full-length AID transcripts and three splice variants by conventional RT-PCR in ~40% of the cases examined. More sensitive, real time quantitative PCR detected AID transcripts in virtually all B-CLL samples tested, although the range of transcript levels was very large between different cases and varied within individual cases over time. Limiting dilution assays revealed that AID expression was restricted to a small fraction of the leukemic cells in the blood. However, this small fraction is not unique in its ability to express AID, as in vitro stimulation of B-CLL cells with appropriate stimuli significantly increased the fraction of AID-expressing cells. These data suggest that AID-mediated DNA alterations may occur in a variably sized, minor subset of B-CLL cells at any given time.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
X. Wu, J. R. Darce, S. K. Chang, G. S. Nowakowski, and D. F. Jelinek
Alternative splicing regulates activation-induced cytidine deaminase (AID): implications for suppression of AID mutagenic activity in normal and malignant B cells
Blood,
December 1, 2008;
112(12):
4675 - 4682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Hauswirth and U. Jager
Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia
Haematologica,
January 1, 2008;
93(1):
14 - 19.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Machida, K. T.-H. Cheng, N. Pavio, V. M.-H. Sung, and M. M. C. Lai
Hepatitis C Virus E2-CD81 Interaction Induces Hypermutation of the Immunoglobulin Gene in B Cells
J. Virol.,
July 1, 2005;
79(13):
8079 - 8089.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. J. Guikema, S. Rosati, K. Akkermans, R. J. Bende, C. J. M. van Noesel, J. H. van Krieken, M. L. Hansmann, E. Schuuring, P. M. Kluin, S. S. Sahota, et al.
Quantitative RT-PCR analysis of activation-induced cytidine deaminase expression in tissue samples from mantle cell lymphoma and B-cell chronic lymphocytic leukemia patients
Blood,
April 1, 2005;
105(7):
2997 - 2999.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pasqualucci, R. Guglielmino, J. Houldsworth, J. Mohr, S. Aoufouchi, R. Polakiewicz, R. S. K. Chaganti, and R. Dalla-Favera
Expression of the AID protein in normal and neoplastic B cells
Blood,
November 15, 2004;
104(10):
3318 - 3325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. K. Stevenson and F. Caligaris-Cappio
Chronic lymphocytic leukemia: revelations from the B-cell receptor
Blood,
June 15, 2004;
103(12):
4389 - 4395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. T. Messmer, E. Albesiano, D. Messmer, and N. Chiorazzi
The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process
Blood,
May 1, 2004;
103(9):
3490 - 3495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. He, A. Chadburn, E. Jou, E. J. Schattner, D. M. Knowles, and A. Cerutti
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL
J. Immunol.,
March 1, 2004;
172(5):
3268 - 3279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
