Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Score, J (Author) Other; Calasanz, MJ (Author) Other; Ottman, O (Author) Other; Pane, F (Author) Other; Yeh, RF (Author) Other; Sobrinho Simoes, M (Author) FMUP; Kreil, S (Author) Other; Ward, D (Author) Other; Hidalgo Curtis, C (Author) Other; Melo, JV (Author) Other; Wiemels, J (Author) Other; Nadel, B (Author) Other; Cross, NCP (Author) Other; Grand, FH (Author) Other

Journal

Title: Leukemia

Vol. 24

Pages: 1742-1750

ISSN: 0887-6924

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-008-Q5N

DOI: 10.1038/leu.2010.174

Abstract (EN): We sought to understand the genesis of the t(9;22) by characterizing genomic breakpoints in chronic myeloid leukemia (CML) and BCR-ABL-positive acute lymphoblastic leukemia (ALL). BCR-ABL breakpoints were identified in p190 ALL (n = 25), p210 ALL (n = 25) and p210 CML (n = 32); reciprocal breakpoints were identified in 54 cases. No evidence for significant clustering and no association with sequence motifs was found except for a breakpoint deficit in repeat regions within BCR for p210 cases. Comparison of reciprocal breakpoints, however, showed differences in the patterns of deletion/insertions between p190 and p210. To explore the possibility that recombinase-activating gene (RAG) activity might be involved in ALL, we performed extra-chromosomal recombination assays for cases with breakpoints close to potential cryptic recombination signal sequence (cRSS) sites. Of 13 ALL cases tested, 1/10 with p190 and 1/3 with p210 precisely recapitulated the forward BCR-ABL breakpoint and 1/10 with p190 precisely recapitulated the reciprocal breakpoint. In contrast, neither of the p210 CMLs tested showed functional cRSSs. Thus, although the t(9;22) does not arise from aberrant variable (V), joining (J) and diversity (D) (V(D) J) recombination, our data suggest that in a subset of ALL cases RAG might create one of the initiating double-strand breaks. Leukemia (2010) 24, 1742-1750;doi: 10.1038/leu.2010.174; published online 12 August 2010

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9