Activation-induced cytidine deaminase splicing patterns in chronic lymphocytic leukemia.
Activation-induced cytidine deaminase (AID) is critically implicated in somatic hypermutation (SHM) and class switch recombination (CSR). AID is expressed as a native transcript and as several splice variants, with as yet undefined roles. Chronic lymphocytic leukemia (CLL) leukemic B cells have also been shown to express AID transcripts, especially in cases with unmutated immunoglobulin (IG) genes. Therefore, AID expression in CLL might potentially be relevant to the disease. The available data on AID-mRNA splicing patterns in CLL are limited and conflicting. Here, we investigated AID-mRNA isoform expression in a series of 195 CLL patients and explored associations with IG gene mutational status and surface immunoglobulin (sIg) isotype expression. Full-length AID transcripts and two splice variants were detected in 110/91/95 cases, respectively. Co-expression of all three AID-mRNA isoforms was significantly more frequent (p<0.001) in cases with unmutated IGHV genes. No significant differences were identified between sIgG vs. sIgMD cases regarding the frequency of AID-mRNA expression. However, expression of at least one AID-mRNA isoform predominated among mutated IgG vs. mutated IgMD cases (p=0.05). These results attest to the biological heterogeneity of CLL and also indicate that AID splice variants may inhibit SHM in CLL cells of the unmutated subtype.
Marantidou
Foteini
F
1st Department of Pathology, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Hematology Department, Nikea General Hospital, Piraeus, Greece.
Dagklis
Antonis
A
Stalika
Evangelia
E
Korkolopoulou
Penelope
P
Korkolopoulou
Panagiota
P
Saetta
Alina
A
Anagnostopoulos
Achilles
A
Laoutaris
Nikolaos
N
Stamatopoulos
Kostas
K
Belessi
Chrysoula
C
Scouras
Zacharias
Z
Patsouris
Efstratios
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D003564:Cytidine Deaminase / Q000235:genetics* / Q000502:physiology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D050441:VDJ Exons / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase