Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols.

Autor: Neumann M; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany. m.neumann@uksh.de.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany. m.neumann@uksh.de.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany. m.neumann@uksh.de., Beder T; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Bastian L; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Hänzelmann S; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany., Bultmann M; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Wolgast N; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Hartmann A; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Trautmann H; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Ortiz-Tanchez J; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany., Schlee C; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany., Schroeder M; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany., Fransecky L; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Vosberg S; Department of Internal Medicine III, University Hospital LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Fiedler W; Medical Department II, Hematology and Oncology, University Hospital Hamburg Eppendorf, Hamburg, Germany., Alakel N; Medical Department I, Carl Gustav Carus University Hospital Dresden, Dresden, Germany., Heberling L; Medical Department I, Carl Gustav Carus University Hospital Dresden, Dresden, Germany., Kondakci M; Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany., Starck M; Medical Department I, Hospital München-Schwabing, Schwabing, Germany., Schwartz S; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany., Raffel S; Medical Department V, University Hospital Heidelberg, Heidelberg, Germany., Müller-Tidow C; Medical Department V, University Hospital Heidelberg, Heidelberg, Germany., Schneller F; Medical Department III, Klinikum rechts der Isar, Technical University Munich, Munich, Germany., Reichle A; Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany., Burmeister T; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany., Greif PA; Department of Internal Medicine III, University Hospital LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Brüggemann M; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany., Gökbuget N; Department of Medicine II, Hematology/Oncology, University Hospital, Goethe University, Frankfurt/M, Germany., Baldus CD; Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.; Clinical Research Unit 'CATCH ALL' (KFO 5010/1), Kiel, Germany.; University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, Kiel and Lübeck, Germany.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Jun; Vol. 38 (6), pp. 1213-1222. Date of Electronic Publication: 2024 May 14.
DOI: 10.1038/s41375-024-02264-0
Abstrakt: In contrast to B-cell precursor acute lymphoblastic leukemia (ALL), molecular subgroups are less well defined in T-lineage ALL. Comprehensive studies on molecular T-ALL subgroups have been predominantly performed in pediatric ALL patients. Currently, molecular characteristics are rarely considered for risk stratification. Herein, we present a homogenously treated cohort of 230 adult T-ALL patients characterized on transcriptome, and partly on DNA methylation and gene mutation level in correlation with clinical outcome. We identified nine molecular subgroups based on aberrant oncogene expression correlating to four distinct DNA methylation patterns. The subgroup distribution differed from reported pediatric T-ALL cohorts with higher frequencies of prognostic unfavorable subgroups like HOXA or LYL1/LMO2. A small subset (3%) of HOXA adult T-ALL patients revealed restricted expression of posterior HOX genes with aberrant activation of lncRNA HOTTIP. With respect to outcome, TLX1 (n = 44) and NKX2-1 (n = 4) had an exceptionally favorable 3-year overall survival (3y-OS) of 94%. Within thymic T-ALL, the non TLX1 patients had an inferior but still good prognosis. To our knowledge this is the largest cohort of adult T-ALL patients characterized by transcriptome sequencing with meaningful clinical follow-up. Risk classification based on molecular subgroups might emerge and contribute to improvements in outcome.
(© 2024. The Author(s).)
Databáze: MEDLINE
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