Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis

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dc.contributor.authorHerold, T.
dc.contributor.authorSchneider, S.
dc.contributor.authorMetzeler, K.
dc.contributor.authorNeumann, M.
dc.contributor.authorHartmann, L.
dc.contributor.authorRoberts, K.
dc.contributor.authorKonstandin, N.
dc.contributor.authorGreif, P.
dc.contributor.authorBraeundl, K.
dc.contributor.authorKsienzyk, B.
dc.contributor.authorHuk, N.
dc.contributor.authorSchneider, I.
dc.contributor.authorZellmeier, E.
dc.contributor.authorJurinovic, V.
dc.contributor.authorMansmann, U.
dc.contributor.authorHiddemann, W.
dc.contributor.authorMullighan, C.
dc.contributor.authorBohlander, S.
dc.contributor.authorSpiekermann, K.
dc.contributor.authorHoelzer, D.
dc.contributor.authoret al.
dc.date.issued2017
dc.description.abstractPhiladelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was a genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult patients (median age: 42 years) with B-cell precursor ALL (BCP-ALL) were classified as having Ph-like ALL using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002) and mutations in JAK2 (7/16; P<0.001) were found exclusively in the Ph-like ALL subgroup. Clinical and outcome analyses were restricted to patients treated in German Multicenter Study Group for Adult ALL (GMALL) trials 06/99 and 07/03 (n=107). The complete remission rate was 100% among both Ph-like ALL patients (n=19) and the "remaining BCP-ALL" cases (n=40), i.e. patients negative for BCR-ABL1 and KMT2A-rearrangements and the Ph-like subtype. Significantly fewer Ph-like ALL patients reached molecular complete remission (33% versus 79%; P=0.02) and had a lower probability of continuous complete remission (26% versus 60%; P=0.03) and overall survival (22% versus 64%; P=0.006) at 5 years compared to the remaining BCP-ALL patients. The profile of genetic lesions in adults with Ph-like ALL, including older adults, resembles that of pediatric Ph-like ALL and differs from the profile in the remaining BCP-ALL. Our study is the first to demonstrate that Ph-like ALL is associated with inferior outcomes in intensively treated older adult patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed. (NCT00199056, NCT00198991).
dc.description.statementofresponsibilityTobias Herold, Stephanie Schneider, Klaus H. Metzeler, Martin Neumann, Luise Hartmann, Kathryn G. Roberts, Nikola P. Konstandin, Philipp A. Greif, Kathrin Bräundl, Bianka Ksienzyk, Natalia Huk, Irene Schneider, Evelyn Zellmeier, Vindi Jurinovic, Ulrich Mansmann, Wolfgang Hiddemann, Charles G. Mullighan, Stefan K. Bohlander, Karsten Spiekermann, Dieter Hoelzer, Monika Brüggemann, Claudia D. Baldus, Martin Dreyling, Nicola Gökbuget
dc.identifier.citationHaematologica, 2017; 102(1):130-138
dc.identifier.doi10.3324/haematol.2015.136366
dc.identifier.issn0390-6078
dc.identifier.issn1592-8721
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/107142
dc.language.isoen
dc.publisherFerrata Storti Foundation
dc.rightsCopyright© Ferrata Storti Foundation
dc.source.urihttps://doi.org/10.3324/haematol.2015.136366
dc.subjectHumans
dc.subjectNeoplasm, Residual
dc.subjectTranslocation, Genetic
dc.subjectReceptors, Cytokine
dc.subjectOncogene Proteins, Fusion
dc.subjectPrognosis
dc.subjectCluster Analysis
dc.subjectSurvival Analysis
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGene Rearrangement
dc.subjectMutation
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectImmunoglobulin Heavy Chains
dc.subjectMale
dc.subjectJanus Kinase 2
dc.subjectPrecursor B-Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectYoung Adult
dc.subjectDNA Copy Number Variations
dc.titleAdults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis
dc.typeJournal article
pubs.publication-statusPublished

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