Characterization of leukemias with ETV6-ABL1 fusion

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dc.contributor.authorZaliova, M.
dc.contributor.authorMoorman, A.V.
dc.contributor.authorCazzaniga, G.
dc.contributor.authorStanulla, M.
dc.contributor.authorHarvey, R.C.
dc.contributor.authorRoberts, K.G.
dc.contributor.authorHeatley, S.L.
dc.contributor.authorLoh, M.L.
dc.contributor.authorKonopleva, M.
dc.contributor.authorChen, I.M.
dc.contributor.authorZimmermannova, O.
dc.contributor.authorSchwab, C.
dc.contributor.authorSmith, O.
dc.contributor.authorMozziconacci, M.J.
dc.contributor.authorChabannon, C.
dc.contributor.authorKim, M.
dc.contributor.authorFrederik Falkenburg, J.H.
dc.contributor.authorNorton, A.
dc.contributor.authorMarshall, K.
dc.contributor.authorHaas, O.A.
dc.contributor.authoret al.
dc.contributor.conferenceAnnual Meeting of the American-Society-of-Hematology (5 Dec 2015 - 8 Dec 2015 : Orlando, FL)
dc.date.issued2016
dc.description.abstractTo 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.
dc.description.statementofresponsibilityMarketa 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
dc.identifier.citationHaematologica, 2016, vol.101, iss.9, pp.1082-1093
dc.identifier.doi10.3324/haematol.2016.144345
dc.identifier.issn0390-6078
dc.identifier.issn1592-8721
dc.identifier.orcidHeatley, S.L. [0000-0001-7497-6477]
dc.identifier.orcidWhite, D. [0000-0003-4844-333X]
dc.identifier.orcidMullighan, C.G. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/103551
dc.language.isoen
dc.publisherFerrata Storti Foundation
dc.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
dc.source.urihttps://doi.org/10.3324/haematol.2016.144345
dc.subjectHumans
dc.subjectLeukemia
dc.subjectTranslocation, Genetic
dc.subjectOncogene Proteins, Fusion
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectCluster Analysis
dc.subjectGene Expression Profiling
dc.subjectAlternative Splicing
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectFemale
dc.subjectMale
dc.subjectProtein-Tyrosine Kinases
dc.subjectYoung Adult
dc.subjectDNA Copy Number Variations
dc.subjectTranscriptome
dc.titleCharacterization of leukemias with ETV6-ABL1 fusion
dc.typeConference paper
pubs.publication-statusPublished

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