Abstract
An immunobiologic approach has led to substantial changes in our current view of chronic lymphocytic leukemia (CLL). Several questions remain unsolved and the definition of the cell origin of CLL is still prominent. The presence of somatic mutations of IGHV genes indicates that, at least in a portion of cases, CLL cells had encountered an antigen during the natural history of the disease. Unmutated (UM) cases show a remarkable skewing in IGHV gene usage. In addition, all CLL cases, both mutated (M) and UM, show a common surface phenotype which is significantly activated and similar to the surface phenotype of antigen (Ag)-experienced B cells. The properties of CLL B-cell receptors (BCR) resemble those observed in normal B cells upon Ag interaction, and gene profiling analyses revealed that both subsets share striking similarities with the so-called memory B cells. The detailed analyses of the complementary determining region 3 (CDR3) sequences of the leukemic immunoglobulin (Ig) receptors showed that unrelated patients in different parts of the world express very similar if not identical BCR. Remarkably, similar VHDJH rearrangements have been identified in both UM- and M-CLL, suggesting an antigenic selection in both subsets of the disease. From all this evidence, the concept has arisen that the cell of origin, regardless its mutational status, has to be "an Ag-experienced" B cell that gives rise to a malignant clone that appears to be more dynamic than previously appreciated and whose progression is favored by a number of molecular and cellular interactions that occur in tissues.
| Original language | English |
|---|---|
| Pages (from-to) | 150-156 |
| Number of pages | 7 |
| Journal | Seminars in Oncology |
| Volume | 33 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2006 |
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ASJC Scopus subject areas
- Oncology
Cite this
The Origin of B-Cell Chronic Lymphocytic Leukemia. / Ghia, Paolo; Caligaris-Cappio, Federico.
In: Seminars in Oncology, Vol. 33, No. 2, 04.2006, p. 150-156.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Origin of B-Cell Chronic Lymphocytic Leukemia
AU - Ghia, Paolo
AU - Caligaris-Cappio, Federico
PY - 2006/4
Y1 - 2006/4
N2 - An immunobiologic approach has led to substantial changes in our current view of chronic lymphocytic leukemia (CLL). Several questions remain unsolved and the definition of the cell origin of CLL is still prominent. The presence of somatic mutations of IGHV genes indicates that, at least in a portion of cases, CLL cells had encountered an antigen during the natural history of the disease. Unmutated (UM) cases show a remarkable skewing in IGHV gene usage. In addition, all CLL cases, both mutated (M) and UM, show a common surface phenotype which is significantly activated and similar to the surface phenotype of antigen (Ag)-experienced B cells. The properties of CLL B-cell receptors (BCR) resemble those observed in normal B cells upon Ag interaction, and gene profiling analyses revealed that both subsets share striking similarities with the so-called memory B cells. The detailed analyses of the complementary determining region 3 (CDR3) sequences of the leukemic immunoglobulin (Ig) receptors showed that unrelated patients in different parts of the world express very similar if not identical BCR. Remarkably, similar VHDJH rearrangements have been identified in both UM- and M-CLL, suggesting an antigenic selection in both subsets of the disease. From all this evidence, the concept has arisen that the cell of origin, regardless its mutational status, has to be "an Ag-experienced" B cell that gives rise to a malignant clone that appears to be more dynamic than previously appreciated and whose progression is favored by a number of molecular and cellular interactions that occur in tissues.
AB - An immunobiologic approach has led to substantial changes in our current view of chronic lymphocytic leukemia (CLL). Several questions remain unsolved and the definition of the cell origin of CLL is still prominent. The presence of somatic mutations of IGHV genes indicates that, at least in a portion of cases, CLL cells had encountered an antigen during the natural history of the disease. Unmutated (UM) cases show a remarkable skewing in IGHV gene usage. In addition, all CLL cases, both mutated (M) and UM, show a common surface phenotype which is significantly activated and similar to the surface phenotype of antigen (Ag)-experienced B cells. The properties of CLL B-cell receptors (BCR) resemble those observed in normal B cells upon Ag interaction, and gene profiling analyses revealed that both subsets share striking similarities with the so-called memory B cells. The detailed analyses of the complementary determining region 3 (CDR3) sequences of the leukemic immunoglobulin (Ig) receptors showed that unrelated patients in different parts of the world express very similar if not identical BCR. Remarkably, similar VHDJH rearrangements have been identified in both UM- and M-CLL, suggesting an antigenic selection in both subsets of the disease. From all this evidence, the concept has arisen that the cell of origin, regardless its mutational status, has to be "an Ag-experienced" B cell that gives rise to a malignant clone that appears to be more dynamic than previously appreciated and whose progression is favored by a number of molecular and cellular interactions that occur in tissues.
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UR - http://www.scopus.com/inward/citedby.url?scp=33645971977&partnerID=8YFLogxK
U2 - 10.1053/j.seminoncol.2006.01.009
DO - 10.1053/j.seminoncol.2006.01.009
M3 - Article
C2 - 16616061
AN - SCOPUS:33645971977
VL - 33
SP - 150
EP - 156
JO - Seminars in Oncology
JF - Seminars in Oncology
SN - 0093-7754
IS - 2
ER -