title: Presence of somatic hypermutation and activation-induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21).
abstract: OBJECTIVE
  Acute lymphoblastic leukemia (ALL) with L2 (FAB) morphology has rarely been reported to show t(14;18)(q32;q21). We aimed to delineate the stage at which this type of ALL is derived in B-lineage differentiation.
  
  
  METHODS
  The somatic hypermutation (SHM) of the variable region of immunoglobulin heavy chain (IgV(H)) gene and the expression of terminal deoxynucleotidyl transferase (TdT), recombination-activating gene 1 and 2 (RAG-1 and -2), and activation-induced cytidine deaminase (AID) were investigated in three cell lines and two fresh samples, including a pair of matched fresh and cell line cells.
  
  
  RESULTS
  TdT, RAG-1, and RAG-2 were variably expressed. AID was expressed in four of five samples. SHM of the IgV(H) gene was found in all samples with high average frequency (11.84%) comparable with that in follicular lymphoma. Ongoing mutation was seen in two fresh samples.
  
  
  CONCLUSIONS
  As AID and SHM are generally regarded as properties exhibited by mature B cells, the presence of AID and SHM in this study seems to be incompatible with the general understanding of the early stage derivation of ALL in B-lineage differentiation. The results here give some insight into the relationship between disease type (ALL or lymphoma) and derivation stage, the overlapping of the early stage phenotype and the mature genomic characteristics, and the probable relationship between the mechanism of the occurrence of t(14;18)(q32;q21) and the machinery causing SHM.
authors.affiliation: International Center for Medical Research (ICMR), Graduate School of Medicine, Kobe University, Kobe, Japan.
authors.forename: Mardiah Suci
authors.initials: MS
authors.lastname: Hardianti
authors.forename: Eiji
authors.initials: E
authors.lastname: Tatsumi
authors.forename: Meilani
authors.initials: M
authors.lastname: Syampurnawati
authors.forename: Kaho
authors.initials: K
authors.lastname: Furuta
authors.forename: Aya
authors.initials: A
authors.lastname: Suzuki
authors.forename: Katsuyasu
authors.initials: K
authors.lastname: Saigo
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
authors.forename: Mariko
authors.initials: M
authors.lastname: Takenokuchi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Tamio
authors.initials: T
authors.lastname: Koizumi
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics*; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D016654:Genes, RAG-1; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C064655:V(D)J recombination activating protein 2; D004253:DNA Nucleotidylexotransferase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase