title: Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis.
abstract: Philadelphia-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).
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany tobias.herold@med.uni-muenchen.de.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Tobias
authors: T
authors: Herold
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Stephanie
authors: S
authors: Schneider
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Klaus H
authors: KH
authors: Metzeler
authors: German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Hematology, Oncology and Tumor Immunology, Charité Universitätsmedizin Berlin, Germany.
authors: Martin
authors: M
authors: Neumann
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Luise
authors: L
authors: Hartmann
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, USA.
authors: Kathryn G
authors: KG
authors: Roberts
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Nikola P
authors: NP
authors: Konstandin
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Philipp A
authors: PA
authors: Greif
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Kathrin
authors: K
authors: Bräundl
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Bianka
authors: B
authors: Ksienzyk
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Natalia
authors: N
authors: Huk
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Irene
authors: I
authors: Schneider
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Evelyn
authors: E
authors: Zellmeier
authors: Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Vindi
authors: V
authors: Jurinovic
authors: Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Ulrich
authors: U
authors: Mansmann
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Wolfgang
authors: W
authors: Hiddemann
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, USA.
authors: Charles G
authors: CG
authors: Mullighan
authors: Department of Molecular Medicine and Pathology, The University of Auckland, New Zealand.
authors: Stefan K
authors: SK
authors: Bohlander
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Karsten
authors: K
authors: Spiekermann
authors: Department of Medicine II, Goethe University Hospital, Frankfurt, Germany.
authors: Dieter
authors: D
authors: Hoelzer
authors: Department of Hematology, University Hospital Schleswig-Holstein Campus Kiel, Germany.
authors: Monika
authors: M
authors: Brüggemann
authors: German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Hematology, Oncology and Tumor Immunology, Charité Universitätsmedizin Berlin, Germany.
authors: Claudia D
authors: CD
authors: Baldus
authors: Department of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany.
authors: Martin
authors: M
authors: Dreyling
authors: Department of Medicine II, Goethe University Hospital, Frankfurt, Germany.
authors: Nicola
authors: N
authors: Gökbuget
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D018121:Receptors, Cytokine / Q000235:genetics*; D016019:Survival Analysis; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C498762:CRLF2 protein, human; D007143:Immunoglobulin Heavy Chains; D015514:Oncogene Proteins, Fusion; D018121:Receptors, Cytokine; C507924:JAK2 protein, human; D053614:Janus Kinase 2