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https://hdl.handle.net/2440/107142
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Type: | Journal article |
Title: | Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis |
Author: | 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. |
Citation: | Haematologica: the hematology journal, 2017; 102(1):130-138 |
Publisher: | Ferrata Storti Foundation |
Issue Date: | 2017 |
ISSN: | 0390-6078 1592-8721 |
Statement of Responsibility: | Tobias 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 |
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). |
Keywords: | Humans Neoplasm, Residual Translocation, Genetic Receptors, Cytokine Oncogene Proteins, Fusion Prognosis Cluster Analysis Survival Analysis Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Rearrangement Mutation Adolescent Adult Middle Aged Female Immunoglobulin Heavy Chains Male Janus Kinase 2 Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Young Adult DNA Copy Number Variations |
Rights: | Copyright© Ferrata Storti Foundation |
DOI: | 10.3324/haematol.2015.136366 |
Published version: | http://dx.doi.org/10.3324/haematol.2015.136366 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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