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Acute Leukemias

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

Leukemia volume 22, pages 1154–1160 (2008)Cite this article

Abstract

Adult T-cell acute lymphoblastic leukemia (T-ALL) continues to represent an unfavorable disease. Molecularly based treatment stratifications could help improve outcome. The prognostic impact of HOX11 and HOX11L2 expression has been an area of controversy. We have investigated 286 adult T-ALL patients enrolled into the German Multicenter ALL (GMALL) therapy protocols by comparative real-time RT-PCR. High HOX11 expression and HOX11L2 expression were predominantly seen in thymic T-ALL (P⩽0.031). In a multivariate analysis HOX11L2 expression proved to be an independent adverse risk factor for relapse-free survival (RFS) with a hazard ratio (HR) of 2.02 (P=0.023) and an HR for overall survival (OS) of 1.81 (P=0.021), both adjusted for the immunophenotype. HOX11 expression was found to have a favorable impact on RFS (HR 0.51; P=0.048) but did not exhibit a significant impact on OS. A subgroup analysis for thymic T-ALL revealed a more pronounced negative correlation of HOX11L2 expression with RFS (HR 3.26; P=0.002) and OS (HR 2.38; P=0.009). Although the prognostic impact of HOX11 in T-ALL is less clear, HOX11L2 expression identifies a small subset of high-risk patients, who are so far classified as standard-risk group. Thus, patients with aberrant HOX11L2 expression should be considered early as candidates for intensified treatment regimes.

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Acknowledgements

We thank A Sindram, M Molkentin, C Seide, P Havemann, B Komischke and R Lippoldt for their work in the molecular and immuncytologic laboratory in Berlin and R Reutzel from the GMALL study board in Frankfurt, as well as all participating centers of the GMALL therapy study. All authors critically read and made contributions to the paper. UB designed research, analyzed data and wrote the paper. NG (head of the GMALL Study Center), analyzed data and edited the paper. SS performed immunophenotyping and edited the paper. HO performed statistical analysis and wrote statistical part of paper. DH (head of the GMALL Study Group) analyzed data and edited the paper. ET (member of the GMALL Study Group) and TB designed research, analyzed data and edited the paper. The authors have no potential conflict of interests to declare.

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Authors and Affiliations

  1. Charité Campus Benjamin Franklin, Medizinische Klinik III, Berlin, Germany

    U Baak, S Schwartz, E Thiel & T Burmeister

  2. Johann Wolfgang Goethe Universität Frankfurt am Main, Medizinische Klinik II, Frankfurt, Germany

    N Gökbuget & D Hoelzer

  3. Charité Campus Mitte, Institut für Biometrie und klinische Epidemiologie, Berlin, Germany

    H Orawa

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Baak, U., Gökbuget, N., Orawa, H. et al. Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group. Leukemia 22, 1154–1160 (2008). https://doi.org/10.1038/leu.2008.52

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