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Acute Leukemias

HOX expression patterns identify a common signature for favorable AML

Leukemia volume 22, pages 2041–2047 (2008)Cite this article

Abstract

Deregulated HOX expression, by chromosomal translocations and myeloid-lymphoid leukemia (MLL) rearrangements, is causal in some types of leukemia. Using real-time reverse transcription-PCR, we examined the expression of 43 clustered HOX, polycomb, MLL and FLT3 genes in 119 newly diagnosed adult acute myeloid leukemias (AMLs) selected from all major cytogenetic groups. Downregulated HOX expression was a consistent feature of favorable AMLs and, among these cases, inv(16) cases had a distinct expression profile. Using a 17-gene predictor in 44 additional samples, we observed a 94.7% specificity for classifying favorable vs intermediate/unfavorable cytogenetic groups. Among other AMLs, HOX overexpression was associated with nucleophosmin (NPM) mutations and we also identified a phenotypically similar subset with wt-NPM. In many unfavorable and other intermediate cytogenetic AMLs, HOX levels resembled those in normal CD34+ cells, except that the homogeneity characteristic of normal samples was not present. We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19ARF suppression may be involved in MLL-associated leukemia. These results underscore the close relationship between HOX expression patterns and certain forms of AML and emphasize the need to determine whether these differences play a role in the disease process.

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Acknowledgements

We thank Drs Hagop Kantarjian and Elihu Estey from the Department of Leukemia (UT-MDA). This work is supported by grants from the National Institutes of Health (CA97710, CA55164 and CA16672) and the Paul and Mary Haas Chair in Genetics (MA).

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Author notes

  1. V Ruvolo, S Gadgil and C Zeng: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Stem Cell Transplantation and Cellular Therapy, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Andreeff, V Ruvolo, W Chen & S Kornblau

  2. Department of Medicine, Division of Hematology-Oncology, University of Colorado Health Sciences Center, Aurora, CO, USA

    S Gadgil

  3. Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Aurora, CO, USA

    C Zeng & A E Barón

  4. Bioinformatics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K Coombes

  5. Department of Medicine, Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC, USA

    H A Drabkin

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  1. M Andreeff
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Correspondence to H A Drabkin.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Andreeff, M., Ruvolo, V., Gadgil, S. et al. HOX expression patterns identify a common signature for favorable AML. Leukemia 22, 2041–2047 (2008). https://doi.org/10.1038/leu.2008.198

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