HOX expression patterns identify a common signature for favorable AML

M. Andreeff, V. Ruvolo, S. Gadgil, C. Zeng, K. Coombes, W. Chen, S. Kornblau, A. E. Barón, H. A. Drabkin

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2041-2047
Number of pages7
JournalLeukemia
Volume22
Issue number11
DOIs
StatePublished - 2008

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Acute Myeloid Leukemia
Lymphoid Leukemia
Myeloid Leukemia
Cytogenetics
Leukemia
Genetic Translocation
Genes
Reverse Transcription
Down-Regulation
Polymerase Chain Reaction
Mutation
nucleophosmin

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Andreeff, M., Ruvolo, V., Gadgil, S., Zeng, C., Coombes, K., Chen, W., ... Drabkin, H. A. (2008). HOX expression patterns identify a common signature for favorable AML. Leukemia, 22(11), 2041-2047. https://doi.org/10.1038/leu.2008.198

HOX expression patterns identify a common signature for favorable AML. / Andreeff, M.; Ruvolo, V.; Gadgil, S.; Zeng, C.; Coombes, K.; Chen, W.; Kornblau, S.; Barón, A. E.; Drabkin, H. A.

In: Leukemia, Vol. 22, No. 11, 2008, p. 2041-2047.

Research output: Contribution to journalArticle

Andreeff, M, Ruvolo, V, Gadgil, S, Zeng, C, Coombes, K, Chen, W, Kornblau, S, Barón, AE & Drabkin, HA 2008, 'HOX expression patterns identify a common signature for favorable AML', Leukemia, vol. 22, no. 11, pp. 2041-2047. https://doi.org/10.1038/leu.2008.198
Andreeff M, Ruvolo V, Gadgil S, Zeng C, Coombes K, Chen W et al. HOX expression patterns identify a common signature for favorable AML. Leukemia. 2008;22(11):2041-2047. https://doi.org/10.1038/leu.2008.198
Andreeff, M. ; Ruvolo, V. ; Gadgil, S. ; Zeng, C. ; Coombes, K. ; Chen, W. ; Kornblau, S. ; Barón, A. E. ; Drabkin, H. A. / HOX expression patterns identify a common signature for favorable AML. In: Leukemia. 2008 ; Vol. 22, No. 11. pp. 2041-2047.
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