| Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia patients. | |
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MedLine Citation:
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PMID: 19759560 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The main reason for the unfavorable clinical outcome of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is genetic instability. However, how normal B-cell precursors acquire the genetic changes that lead to transformation has not yet been completely defined. We investigated the expression of the activation-induced cytidine deaminase (AID) and its role in clinical outcome in 61 adult BCR-ABL1-positive ALL patients. AID expression was detected in 36 patients (59%); it correlated with the BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors. Different AID splice variants were identified: full-length isoform; AIDDeltaE4a, with a 30-bp deletion of exon 4; AIDDeltaE4, with the exon 4 deletion; AIDins3, with the retention of intron 3; AIDDeltaE3-E4 isoform without deaminase activity. AID-FL predominantly showed cytoplasmic localization, as did the AID-DeltaE4a and AID-DeltaE3E4 variants, whereas the C-terminal-truncated AID-DeltaE4 showed a slightly increased nuclear localization pattern. AID expression correlated with a higher number of copy number alterations identified in genome-wide analysis using a single-nucleotide polymorphism array. However, the expression of AID at diagnosis was not associated with a worse prognosis. In conclusion, BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that may act as mutators outside the immunoglobulin (Ig) gene loci in promoting genetic instability. |
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Authors:
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I Iacobucci; A Lonetti; F Messa; A Ferrari; D Cilloni; S Soverini; F Paoloni; F Arruga; E Ottaviani; S Chiaretti; M Messina; M Vignetti; C Papayannidis; A Vitale; F Pane; P P Piccaluga; S Paolini; G Berton; A Baruzzi; G Saglio; M Baccarani; R Foà; G Martinelli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-17 |
Journal Detail:
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Title: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K Volume: 24 ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-13 Completed Date: 2010-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 66-73 Citation Subset: IM |
Affiliation:
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Department of Institute of Hematology and Medical Oncology, L and A Seràgnoli S Orsola Malpighi Hospital, University of Bologna, Bologna 9-40138, Italy. giovanni.martinelli2@unibo.it |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Alternative Splicing Cytidine Deaminase / genetics*, physiology DNA Breaks, Single-Stranded Fusion Proteins, bcr-abl / analysis*, genetics Genes, Immunoglobulin Humans Isoenzymes / genetics* Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology*, genetics Prognosis RNA, Messenger / analysis |
| Chemical | |
Reg. No./Substance:
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0/Fusion Proteins, bcr-abl; 0/Isoenzymes; 0/RNA, Messenger; 0/abl-bcr fusion protein, human; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
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