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

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 f...

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Main Authors: Neumann, Martin (Author) , Beder, Thomas (Author) , Bastian, Lorenz (Author) , Hänzelmann, Sonja (Author) , Bultmann, Miriam (Author) , Wolgast, Nadine (Author) , Hartmann, Alina (Author) , Trautmann, Heiko (Author) , Ortiz-Tanchez, Jutta (Author) , Schlee, Cornelia (Author) , Schroeder, Michael (Author) , Fransecky, Lars (Author) , Vosberg, Sebastian (Author) , Fiedler, Walter (Author) , Alakel, Nael (Author) , Heberling, Lisa (Author) , Kondakci, Mustafa (Author) , Starck, Michael (Author) , Schwartz, Stefan (Author) , Raffel, Simon (Author) , Müller-Tidow, Carsten (Author) , Schneller, Folker (Author) , Reichle, Albrecht (Author) , Burmeister, Thomas (Author) , Greif, Philipp A. (Author) , Brüggemann, Monika (Author) , Gökbuget, Nicola (Author) , Baldus, Claudia D. (Author)
Format: Article (Journal)
Language:English
Published: 14 May 2024
In: Leukemia
Year: 2024, Volume: 38, Issue: 6, Pages: 1213-1222
ISSN:1476-5551
DOI:10.1038/s41375-024-02264-0
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-024-02264-0
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-024-02264-0
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Author Notes:Martin Neumann, Thomas Beder, Lorenz Bastian, Sonja Hänzelmann, Miriam Bultmann, Nadine Wolgast, Alina Hartmann, Heiko Trautmann, Jutta Ortiz-Tanchez, Cornelia Schlee, Michael Schroeder, Lars Fransecky, Sebastian Vosberg, Walter Fiedler, Nael Alakel, Lisa Heberling, Mustafa Kondakci, Michael Starck, Stefan Schwartz, Simon Raffel, Carsten Müller-Tidow, Folker Schneller, Albrecht Reichle, Thomas Burmeister, Philipp A. Greif, Monika Brüggemann, Nicola Gökbuget and Claudia D. Baldus
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Summary: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.
Item Description:Gesehen am 25.11.2024
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/s41375-024-02264-0

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