Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia patients.

Abstract:

: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.

journal_name

Leukemia

journal_title

Leukemia

authors

Iacobucci I,Lonetti A,Messa F,Ferrari A,Cilloni D,Soverini S,Paoloni F,Arruga F,Ottaviani E,Chiaretti S,Messina M,Vignetti M,Papayannidis C,Vitale A,Pane F,Piccaluga PP,Paolini S,Berton G,Baruzzi A,Saglio G,Baccar

doi

10.1038/leu.2009.197

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

66-73

issue

1

eissn

0887-6924

issn

1476-5551

pii

leu2009197

journal_volume

24

pub_type

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