title: Aberrant activation-induced cytidine deaminase expression in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.
abstract: Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and plays a critical role in somatic hypermutation and class-switch recombination of immunoglobulin genes. Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carries a poor prognosis and is specifically treated with tyrosine kinase inhibitors. Interestingly, AID has been shown to be aberrantly expressed and functional in Ph+ ALL and is thought to contribute to genetic instability. We hypothesized that AID might be detectable in routinely processed bone marrow biopsies by immunohistochemistry (IHC) and assist in identifying Ph+ ALL. We found that AID was expressed in 26 (70%) of 37 cases of Ph+ ALL but only 1 (2.9%) of 38 cases of Ph- ALL cases. There was a significant difference in AID expression between these 2 ALL groups (P < .001, Fisher exact test). The expression of AID was confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) and correlated with IHC scoring. AID protein is expressed in a large proportion of Ph+ ALL cases at levels detectable by IHC in clinical samples and might be useful to rapidly identify cases likely to have a BCR/ABL1 fusion.
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, L-11, Cleveland, OH, USA 44195. Electronic address: yangshi11@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, L-11, Cleveland, OH, USA 44195. Electronic address: Zhaox2@ccf.org.
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, L-11, Cleveland, OH, USA 44195. Electronic address: durkinl@ccf.org.
authors.forename: Lisa
authors.initials: L
authors.lastname: Durkin
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, L-11, Cleveland, OH, USA 44195. Electronic address: Rogersj5@ccf.org.
authors.forename: Heesun Joyce
authors.initials: HJ
authors.lastname: Rogers
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, L-11, Cleveland, OH, USA 44195. Electronic address: hsie@ccf.org.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D001856:Bone Marrow Examination; D002648:Child; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000032:analysis* / Q000235:genetics; D020732:Cytogenetic Analysis; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D014408:Biomarkers, Tumor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: Activation-induced cytidine deaminase; Acute lymphoblastic leukemia; BCR-ABL1; Immunohistochemistry; Philadelphia chromosome