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

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Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols. / Neumann, Martin; Beder, Thomas; Bastian, Lorenz; Hänzelmann, Sonja; Bultmann, Miriam; Wolgast, Nadine; Hartmann, Alina; Trautmann, Heiko; Ortiz-Tanchez, Jutta; Schlee, Cornelia; Schroeder, Michael; Fransecky, Lars; Vosberg, Sebastian; Fiedler, Walter; Alakel, Nael; Heberling, Lisa; Kondakci, Mustafa; Starck, Michael; Schwartz, Stefan; Raffel, Simon; Müller-Tidow, Carsten; Schneller, Folker; Reichle, Albrecht; Burmeister, Thomas; Greif, Philipp A; Brüggemann, Monika; Gökbuget, Nicola; Baldus, Claudia D.

In: LEUKEMIA, Vol. 38, No. 6, 06.2024, p. 1213-1222.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Neumann, M, Beder, T, Bastian, L, Hänzelmann, S, Bultmann, M, Wolgast, N, Hartmann, A, Trautmann, H, Ortiz-Tanchez, J, Schlee, C, Schroeder, M, Fransecky, L, Vosberg, S, Fiedler, W, Alakel, N, Heberling, L, Kondakci, M, Starck, M, Schwartz, S, Raffel, S, Müller-Tidow, C, Schneller, F, Reichle, A, Burmeister, T, Greif, PA, Brüggemann, M, Gökbuget, N & Baldus, CD 2024, 'Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols', LEUKEMIA, vol. 38, no. 6, pp. 1213-1222. https://doi.org/10.1038/s41375-024-02264-0

APA

Neumann, M., Beder, T., Bastian, L., Hänzelmann, S., Bultmann, M., Wolgast, N., Hartmann, A., Trautmann, H., Ortiz-Tanchez, J., Schlee, C., Schroeder, M., Fransecky, L., Vosberg, S., Fiedler, W., Alakel, N., Heberling, L., Kondakci, M., Starck, M., Schwartz, S., ... Baldus, C. D. (2024). Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols. LEUKEMIA, 38(6), 1213-1222. https://doi.org/10.1038/s41375-024-02264-0

Vancouver

Neumann M, Beder T, Bastian L, Hänzelmann S, Bultmann M, Wolgast N et al. Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols. LEUKEMIA. 2024 Jun;38(6):1213-1222. https://doi.org/10.1038/s41375-024-02264-0

Bibtex

@article{18ca9265f8de419b9537d13ca0346920,
title = "Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols",
abstract = "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.",
keywords = "Humans, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Adult, Male, Female, Prognosis, Middle Aged, Young Adult, Adolescent, DNA Methylation, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Aged, Biomarkers, Tumor/genetics, Mutation, Follow-Up Studies, Survival Rate, Transcriptome, Homeodomain Proteins/genetics",
author = "Martin Neumann and Thomas Beder and Lorenz Bastian and Sonja H{\"a}nzelmann and Miriam Bultmann and Nadine Wolgast and Alina Hartmann and Heiko Trautmann and Jutta Ortiz-Tanchez and Cornelia Schlee and Michael Schroeder and Lars Fransecky and Sebastian Vosberg and Walter Fiedler and Nael Alakel and Lisa Heberling and Mustafa Kondakci and Michael Starck and Stefan Schwartz and Simon Raffel and Carsten M{\"u}ller-Tidow and Folker Schneller and Albrecht Reichle and Thomas Burmeister and Greif, {Philipp A} and Monika Br{\"u}ggemann and Nicola G{\"o}kbuget and Baldus, {Claudia D}",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jun,
doi = "10.1038/s41375-024-02264-0",
language = "English",
volume = "38",
pages = "1213--1222",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols

AU - Neumann, Martin

AU - Beder, Thomas

AU - Bastian, Lorenz

AU - Hänzelmann, Sonja

AU - Bultmann, Miriam

AU - Wolgast, Nadine

AU - Hartmann, Alina

AU - Trautmann, Heiko

AU - Ortiz-Tanchez, Jutta

AU - Schlee, Cornelia

AU - Schroeder, Michael

AU - Fransecky, Lars

AU - Vosberg, Sebastian

AU - Fiedler, Walter

AU - Alakel, Nael

AU - Heberling, Lisa

AU - Kondakci, Mustafa

AU - Starck, Michael

AU - Schwartz, Stefan

AU - Raffel, Simon

AU - Müller-Tidow, Carsten

AU - Schneller, Folker

AU - Reichle, Albrecht

AU - Burmeister, Thomas

AU - Greif, Philipp A

AU - Brüggemann, Monika

AU - Gökbuget, Nicola

AU - Baldus, Claudia D

N1 - © 2024. The Author(s).

PY - 2024/6

Y1 - 2024/6

N2 - 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.

AB - 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.

KW - Humans

KW - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics

KW - Adult

KW - Male

KW - Female

KW - Prognosis

KW - Middle Aged

KW - Young Adult

KW - Adolescent

KW - DNA Methylation

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Aged

KW - Biomarkers, Tumor/genetics

KW - Mutation

KW - Follow-Up Studies

KW - Survival Rate

KW - Transcriptome

KW - Homeodomain Proteins/genetics

U2 - 10.1038/s41375-024-02264-0

DO - 10.1038/s41375-024-02264-0

M3 - SCORING: Journal article

C2 - 38744920

VL - 38

SP - 1213

EP - 1222

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 6

ER -