Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/103551
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Type: Conference paper
Title: Characterization of leukemias with ETV6-ABL1 fusion
Author: Zaliova, M.
Moorman, A.
Cazzaniga, G.
Stanulla, M.
Harvey, R.
Roberts, K.
Heatley, S.
Loh, M.
Konopleva, M.
Chen, I.
Zimmermannova, O.
Schwab, C.
Smith, O.
Mozziconacci, M.
Chabannon, C.
Kim, M.
Frederik Falkenburg, J.
Norton, A.
Marshall, K.
Haas, O.
Starkova, J.
Stuchly, J.
Hunger, S.
White, D.
Mullighan, C.
Willman, C.
Stary, J.
Trka, J.
Zuna, J.
Citation: Proceedings of the 57th Annual Meeting of the American-Society-of-Hematology, as published in Haematologica, 2016 / vol.101, iss.9, pp.1082-1093
Publisher: Ferrata Storti Foundation
Issue Date: 2016
ISSN: 0390-6078
1592-8721
Conference Name: Annual Meeting of the American-Society-of-Hematology (05 Dec 2015 - 08 Dec 2015 : Orlando, FL)
Statement of
Responsibility: 
Marketa Zaliova, Anthony V. Moorman, Giovanni Cazzaniga, Martin Stanulla, Richard C. Harvey, Kathryn G. Roberts, Sue L. Heatley, Mignon L. Loh, Marina Konopleva, I-Ming Chen, Olga Zimmermannova, Claire Schwab, Owen Smith, Marie-Joelle Mozziconacci, Christian Chabannon, Myungshin Kim, J. H. Frederik Falkenburg, Alice Norton, Karen Marshall, Oskar A. Haas, Julia Starkova, Jan Stuchly, Stephen P. Hunger, Deborah White, Charles G. Mullighan, Cheryl L. Willman, Jan Stary, Jan Trka, and Jan Zuna
Abstract: To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with tyrosine kinase inhibitors should be considered for patients with this fusion.
Keywords: Humans; Leukemia; Translocation, Genetic; Oncogene Proteins, Fusion; In Situ Hybridization, Fluorescence; Cluster Analysis; Gene Expression Profiling; Alternative Splicing; Phenotype; Polymorphism, Single Nucleotide; Adolescent; Adult; Aged; Middle Aged; Child; Child, Preschool; Infant; Female; Male; Protein-Tyrosine Kinases; Young Adult; DNA Copy Number Variations; Transcriptome
Rights: © 2016 Ferrata Storti Foundation. Material published in Haematologica is covered by copyright. All rights reserved to the Ferrata Storti Foundation. Copies of articles are allowed for personal or internal use. Permission in writing from the publisher is required for any other use. Haematologica is an Open Access journal
RMID: 0030046096
DOI: 10.3324/haematol.2016.144345
Appears in Collections:Pathology publications

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