TY - JOUR
T1 - IGHV gene insertions and deletions in chronic lymphocytic leukemia
T2 - "CLL-biased" deletions in a subset of cases with stereotyped receptors
AU - Belessi, Chrysoula J.
AU - Davi, Frédéric B.
AU - Stamatopoulos, Kostas E.
AU - Degano, Massimo
AU - Andreou, Thanassis M.
AU - Moreno, Carol
AU - Merle-Béral, Hélène
AU - Crespo, Marta
AU - Laoutaris, Nikolaos P.
AU - Montserrat, Emili
AU - Caligaris-Cappio, Federico
AU - Anagnostopoulos, Achilles Z.
AU - Ghia, Paolo
PY - 2006/7
Y1 - 2006/7
N2 - Nucleotide insertions/duplications or deletions in immunoglobulin heavy chain genes have been found in 24/760 patients (3.15%) with chronic lymphocytic leukemia (CLL). In 21/24 cases, the inserted/duplicated or lost nucleotides occurred in multiples of 3; therefore, the original reading frame was maintained and a potentially intact receptor was coded. The pattern and location of insertions/duplications or deletions in CLL and their restriction to mutated IGHV rearranged genes strongly suggests that they resulted from somatic hypermutation. Their incidence in CLL is consistent with previous reports in normal, auto-reactive and neoplastic human B cells, thus seemingly indicating that these modifications generally arise without any particular disease-specific associations. A striking exception to this rule was identified in CLL IGHV3-21-expressing cases: one amino acid was deleted from the CDR2 region in 16/63 (25.4%) mutated CLL IGHV3-21 sequences (including public database-derived IGHV3-21 CLL cases + the present series) vs. only 2/257 (0.78%) public database-derived mutated non-CLL IGHV3-21 sequences; 15/ 16 CLL IGHV3-21 sequences carrying this deletion belonged to a subset with unique, shared HCDR3 and light chain CDR3 motifs. This finding further supports the idea of selective antigenic pressures playing a pathogenetic role in some CLL cases.
AB - Nucleotide insertions/duplications or deletions in immunoglobulin heavy chain genes have been found in 24/760 patients (3.15%) with chronic lymphocytic leukemia (CLL). In 21/24 cases, the inserted/duplicated or lost nucleotides occurred in multiples of 3; therefore, the original reading frame was maintained and a potentially intact receptor was coded. The pattern and location of insertions/duplications or deletions in CLL and their restriction to mutated IGHV rearranged genes strongly suggests that they resulted from somatic hypermutation. Their incidence in CLL is consistent with previous reports in normal, auto-reactive and neoplastic human B cells, thus seemingly indicating that these modifications generally arise without any particular disease-specific associations. A striking exception to this rule was identified in CLL IGHV3-21-expressing cases: one amino acid was deleted from the CDR2 region in 16/63 (25.4%) mutated CLL IGHV3-21 sequences (including public database-derived IGHV3-21 CLL cases + the present series) vs. only 2/257 (0.78%) public database-derived mutated non-CLL IGHV3-21 sequences; 15/ 16 CLL IGHV3-21 sequences carrying this deletion belonged to a subset with unique, shared HCDR3 and light chain CDR3 motifs. This finding further supports the idea of selective antigenic pressures playing a pathogenetic role in some CLL cases.
KW - Antigen receptors
KW - B cells
KW - Cancer
KW - Immunoglobulins
KW - V(D)J recombination
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U2 - 10.1002/eji.200535751
DO - 10.1002/eji.200535751
M3 - Article
C2 - 16783849
AN - SCOPUS:33746238516
VL - 36
SP - 1963
EP - 1974
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 7
ER -