High expression of activation-induced cytidine deaminase (AID) and splice variants is a distinctive feature of poor-prognosis chronic lymphocytic leukemia.
In chronic lymphocytic leukemia (CLL), analysis of immunoglobulin heavy chain variable regions for somatic hypermutation identifies 2 prognostic subsets, mutated and unmutated. Investigators have postulated that unmutated and mutated CLL arises from malignant transformation of pre- and post-germinal center (GC) B cells, respectively. Alternatively, unmutated cases may arise from B cells stimulated by T-cell-independent antigens or from GC B cells with inactive somatic hypermutation. Activation-induced cytidine deaminase (AID), a protein essential for somatic hypermutation, is expressed by GC B cells in which this process occurs. We investigated AID mRNA expression in 20 CLL cases. In 8 cases we detected high expression of wild-type AID mRNA and 2 splice variants; in 12 cases and 5 normal peripheral blood B-cell samples we detected no expression using standard conditions. Of 8 CLL cases that highly expressed AID, 7 were unmutated, suggesting that this subset may arise from GC-experienced B cells with inactive somatic hypermutation, and may predict prognosis.
McCarthy
Helen
H
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Wierda
William G
WG
Barron
Lynn L
LL
Cromwell
Candy C
CC
Wang
Jing
J
Coombes
Kevin R
KR
Rangel
Roberto
R
Elenitoba-Johnson
Kojo S J
KS
Keating
Michael J
MJ
Abruzzo
Lynne V
LV
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D003564:Cytidine Deaminase