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Acute Leukemias

BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia

Leukemia volume 24, pages 1429–1436 (2010)Cite this article

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Abstract

Over expression of BAALC (brain and acute leukemia, cytoplasmic) predicts an inferior outcome in acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. To identify BAALC-associated genes that give insights into its functional role in chemotherapy resistance, gene expression signatures differentiating high from low BAALC expressers were generated from normal CD34+ progenitors, T-acute lymphoblastic leukemia (T-ALL) and AML samples. The insulin-like growth factor binding protein 7 (IGFBP7) was one of the four genes (CD34, CD133, natriuretic peptide receptor C (NPR3), IGFBP7) coexpressed with BAALC and common to the three entities. In T-ALL, high IGFBP7-expression was associated with an immature phenotype of early T-ALL (P<0.001), expression of CD34 (P<0.001) and CD33 (P<0.001). Moreover, high IGFBP7-expression predicted primary therapy resistance (P=0.03) and inferior survival in T-ALL (P=0.03). In vitro studies revealed that IGFBP7 protein significantly inhibited the proliferation of leukemia cell lines (Jurkat cells: 42% reduction, P=0.002; KG1a cells: 65% reduction, P<0.001). In conclusion, IGFBP7 was identified as a BAALC coexpressed gene. Furthermore, high IGFBP7 was associated with stem cell features and treatment failure in T-ALL. In contrast to BAALC, which likely represents only a surrogate marker of treatment failure in acute leukemia, IGFBP7 regulates the proliferation of leukemic cells and might be involved in chemotherapy resistance.

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Acknowledgements

We want to thank Liliana Mochmann for critical reading of the paper and Daniel Nowak for the technical support. We also thank all the members of the German multicenter acute lymphoblastic leukemia study group for their support, and the participating centers for enrolling patients and providing the clinical data. Funding: This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) to CDB.

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Authors and Affiliations

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

    S Heesch, C Schlee, M Neumann, A Kühnl, S Schwartz, E Thiel & C D Baldus

  2. Freie Universität Berlin, Institut für Biologie, Chemie und Pharmazie, Berlin, Germany

    S Heesch

  3. Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Institut für Biometrie und klinische Epidemiologie, Berlin, Germany

    A Stroux

  4. MLL Münchner Leukämie Labor, M, ü, nchen, Germany

    T Haferlach

  5. Johann Wolfgang Goethe-Universität, Medizinische Klinik II, Frankfurt/Main, Germany

    N Goekbuget & D Hoelzer

  6. Universität Heidelberg, Medizinische Fakultät Mannheim, Medizinische Klinik III, Mannheim, Germany

    W-K Hofmann

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Correspondence to C D Baldus.

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Competing interests

The microarray innovations in leukemia study was in part supported by Roche Molecular Systems. TH is a part owner of the MLL Münchner Leukämie Labor GmbH. The other authors declare no conflict of interest.

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Heesch, S., Schlee, C., Neumann, M. et al. BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia. Leukemia 24, 1429–1436 (2010). https://doi.org/10.1038/leu.2010.130

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