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The surface molecule signature of primary human acute myeloid leukemia (AML) cells is highly associated with NPM1 mutation status

Leukemia volume 26, pages 557–559 (2012)Cite this article

Even though human acute myeloid leukemia (AML) is characterized by an expansion of malignant myeloblasts, these immature leukemic cells can show signs of differentiation both by morphological examination and by flow-cytometric analysis of membrane molecules.1 Analysis of this molecular profile is mainly used as a diagnostic tool to detect panmyeloid or lineage-associated differentiation markers, and thereby distinguish between myeloblasts and lymphoid blasts.2 On the other hand, cytogenetic and molecular genetic analyses are mainly used for prognostic classification of patients. The most important mutations are then FLT3-ITD, which has an adverse prognostic impact, and NPM-1 mutations, which can be associated with a favorable prognosis.2 Certain cytogenetic and molecular genetic abnormalities are associated with signs of AML cell differentiation, including NPM-1 mutations, which are associated with monocytic morphology and low expression of the CD34 stem cell marker.3 These last observations suggest that the cell of origin of the NPM-1 mutation is a myeloid progenitor and not the most immature stem cells. In this context we have therefore investigated in more detail the associations between NPM-1 mutations and AML cell differentiation as defined by a limited number of well-characterized surface membrane molecules.

The membrane molecule profile was investigated by flow cytometry for 184 consecutive AML patients. All patients were examined with regard to the expression of CD11c (expressed on monocytes), CD13 (monocytes, neutrophils), CD14 (mainly expressed on monocytes, at lower levels on neutrophils), CD15 (mainly neutrophils, also monocytes), CD33 (appears on myelomonocytic precursors after CD34), CD34 (immature hematopoietic cells), CD45 (leukocytes) and HLA-DR.4 The French–American–British (FAB) classification was used for morphological evaluation of the differentiation status,5 and analysis for FLT3 and NPM-1 mutations was performed as previously described.6 Bioinformatical analyses were performed using the J-Express 2009 analysis suite (MolMine AS, Bergen, Norway)7 and hierarchical clustering was performed with Pearson's correlation as distance measure and complete weighted linkage.

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Acknowledgements

This study received financial support from the Norwegian Cancer Association.

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Authors and Affiliations

  1. Department of Medicine, Haukeland University Hospital, Bergen, Norway

    G Tsykunova & Ø Bruserud

  2. Division for Hematology, Institute of Medicine, University of Bergen, Bergen, Norway

    H Reikvam & Ø Bruserud

  3. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    R Hovland

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  1. G Tsykunova
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  2. H Reikvam
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  4. Ø Bruserud
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Correspondence to Ø Bruserud.

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Tsykunova, G., Reikvam, H., Hovland, R. et al. The surface molecule signature of primary human acute myeloid leukemia (AML) cells is highly associated with NPM1 mutation status. Leukemia 26, 557–559 (2012). https://doi.org/10.1038/leu.2011.243

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