Herold, T.Schneider, S.Metzeler, K.Neumann, M.Hartmann, L.Roberts, K.Konstandin, N.Greif, P.Braeundl, K.Ksienzyk, B.Huk, N.Schneider, I.Zellmeier, E.Jurinovic, V.Mansmann, U.Hiddemann, W.Mullighan, C.Bohlander, S.Spiekermann, K.Hoelzer, D.et al.2017-08-232017-08-232017Haematologica, 2017; 102(1):130-1380390-60781592-8721http://hdl.handle.net/2440/107142Philadelphia-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).enCopyright© Ferrata Storti FoundationHumansNeoplasm, ResidualTranslocation, GeneticReceptors, CytokineOncogene Proteins, FusionPrognosisCluster AnalysisSurvival AnalysisGene Expression ProfilingGene Expression Regulation, NeoplasticGene RearrangementMutationAdolescentAdultMiddle AgedFemaleImmunoglobulin Heavy ChainsMaleJanus Kinase 2Precursor B-Cell Lymphoblastic Leukemia-LymphomaYoung AdultDNA Copy Number VariationsJournal article003006161610.3324/haematol.2015.1363660003929218000262-s2.0-85008323482282663Mullighan, C. [0000-0002-1871-1850]