Abstract
Bone marrow samples from 43 adult patients with de novo diagnosed acute myeloid leukemia (AML) – 10 acute promyelocytic leukemias (APL) with t(15;17), four AML with inv(16), seven monocytic leukemias and 22 nonmonocytic leukemias – were analyzed using high-density oligonucleotide microarrays. Hierarchical clustering analysis segregated APL, AML with inv(16), monocytic leukemias and the remaining AML into separate groups. A set of only 21 genes was able to assign AML to one of these three classes: APL, inv(16) and other AML subtype without a specific translocation. Quantitative RT-PCR performed for 18 out of these predictor genes confirmed microarray results. APL expressed high levels of FGF13 and FGFR1 as well as two potent angiogenic factors, HGF and VEGF. AML with inv(16) showed an upregulation of MYH11 and a downregulation of a gene encoding a core-binding factor protein, RUNX3. Genes involved in cell adhesion represented the most altered functional category in monocytic leukemias. Two major groups emerged from the remaining 22 AML: cluster A with 10 samples and cluster B with 12. All the eight leukemias that were either refractory to treatment or that relapsed afterwards were assigned to cluster B. In the latter cluster, CD34 upregulation and serine proteases downregulation is consistent with a maturation arrest and lack of granulocytic differentiation.
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Acknowledgements
We thank Mark Anderson of the University Technology Transfer Office and M Ángeles Hernández, Amador Crego, Ana Simón, Laura Hierro and Estela Hernández for technical assistance. We are grateful to Fenghuang Zhan and John Shaughnessy for technical support on microarray analysis. This study was partially supported by ‘Ministerio de Ciencia y Tecnología’ Grant (SAF2001-1687) and Spanish FIS Grant (02/1358). NCG, RLP and JLG were partially supported by grants from ‘Fundación Española de Hematología y Hemoterapia’, ‘Asociación Española contra el Cáncer’ and Spanish FIS (01/3153), respectively.
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Gutiérrez, N., López-Pérez, R., Hernández, J. et al. Gene expression profile reveals deregulation of genes with relevant functions in the different subclasses of acute myeloid leukemia. Leukemia 19, 402–409 (2005). https://doi.org/10.1038/sj.leu.2403625
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DOI: https://doi.org/10.1038/sj.leu.2403625
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