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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2159-2167. Prepublished online as a Blood First Edition Paper on July 9, 2009; DOI 10.1182/blood-2008-08-173963. This Article Full Text Full Text (PDF) Supplemental Appendix and Tables Additional Supplemental Tables and Supplemental Figures All Versions of this Article: blood-2008-08-173963v1 114/10/2159    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Iacobucci, I. Articles by Martinelli, G. PubMed PubMed Citation Articles by Iacobucci, I. Articles by Martinelli, G. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCR-ABL1–positive acute lymphoblastic leukemia patients: on behalf of Gruppo Italiano Malattie Ematologiche dell'Adulto Acute Leukemia Working Party (GIMEMA AL WP) Ilaria Iacobucci1, Clelia Tiziana Storlazzi2, Daniela Cilloni3, Annalisa Lonetti1, Emanuela Ottaviani1, Simona Soverini1, Annalisa Astolfi4, Sabina Chiaretti5, Antonella Vitale5, Francesca Messa3, Luciana Impera2, Carmen Baldazzi1, Pietro D'Addabbo2, Cristina Papayannidis1, Angelo Lonoce2, Sabrina Colarossi1, Marco Vignetti5, Pier Paolo Piccaluga1, Stefania Paolini1, Domenico Russo6, Fabrizio Pane7, Giuseppe Saglio3, Michele Baccarani1, Robin Foà5, and Giovanni Martinelli1 1 Department of Hematology/Oncology L and A Seràgnoli S Orsola Malpighi Hospital, University of Bologna, Bologna; 2 Department of Genetics and Microbiology, University of Bari, Bari; 3 Department of Clinical and Biological Science, University of Turin at Orbassano, Turin; 4 Pediatric Oncology and Hematology L Seràgnoli, Bologna; 5 Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome; 6 Hematology and Bone Marrow Transplantation Unit, Spedali Civili Hospital, University of Brescia, Brescia; and 7 CEINGE Biotecnologie Avanzate and Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy The BCR-ABL1 fusion gene defines the subgroup of acute lymphoblastic leukemia (ALL) with the worst clinical prognosis. To identify oncogenic lesions that combine with BCR-ABL1 to cause ALL, we used Affymetrix Genome-Wide Human SNP arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic polymerase chain reaction to study 106 cases of adult BCR-ABL1–positive ALL. The most frequent somatic copy number alteration was a focal deletion on 7p12 of IKZF1, which encodes the transcription factor Ikaros and was identified in 80 (75%) of 106 patients. Different patterns of deletions occurred, but the most frequent were those characterized by a loss of exons 4 through 7 (4-7) and by removal of exons 2 through 7 (2-7). A variable number of nucleotides (patient specific) were inserted at the conjunction and maintained with fidelity at the time of relapse. The extent of the 4-7 deletion correlated with the expression of a dominant-negative isoform with cytoplasmic localization and oncogenic activity, whereas the 2-7 deletion resulted in a transcript lacking the translation start site. The IKZF1 deletion also was identified in the progression of chronic myeloid leukemia to lymphoid blast crisis (66%) but never in myeloid blast crisis or chronic-phase chronic myeloid leukemia or in patients with acute myeloid leukemia. Known DNA sequences and structural features were mapped along the breakpoint cluster regions, including heptamer recombination signal sequences recognized by RAG enzymes during V(D)J recombination, suggesting that IKZF1 deletions could arise from aberrant RAG-mediated recombination. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Martinelli, I. Iacobucci, C. T. Storlazzi, M. Vignetti, F. Paoloni, D. Cilloni, S. Soverini, A. Vitale, S. Chiaretti, G. Cimino, et al. IKZF1 (Ikaros) Deletions in BCR-ABL1-Positive Acute Lymphoblastic Leukemia Are Associated With Short Disease-Free Survival and High Rate of Cumulative Incidence of Relapse: A GIMEMA AL WP Report J. Clin. Oncol., November 1, 2009; 27(31): 5202 - 5207. [Abstract] [Full Text] [PDF]

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