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DNA microarray analysis of natural killer cell-type lymphoproliferative disease of granular lymphocytes with purified CD3−CD56+ fractions

Leukemia volume 18, pages 556–565 (2004)Cite this article

Abstract

Natural killer (NK) cell-type lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the outgrowth of CD3−CD16/56+ NK cells, and can be further subdivided into two distinct categories: aggressive NK cell leukemia (ANKL) and chronic NK lymphocytosis (CNKL). To gain insights into the pathophysiology of NK cell-type LDGL, we here purified CD3−CD56+ fractions from healthy individuals (n=9) and those with CNKL (n=9) or ANKL (n=1), and compared the expression profiles of >12 000 genes. A total of 15 ‘LDGL-associated genes’ were identified, and a correspondence analysis on such genes could clearly indicate that LDGL samples share a ‘molecular signature’ distinct from that of normal NK cells. With a newly invented class prediction algorithm, ‘weighted distance method’, all 19 samples received a clinically matched diagnosis, and, furthermore, a detailed cross-validation trial for the prediction of normal or CNKL status could achieve a high accuracy (77.8%). By applying another statistical approach, we could extract other sets of genes, expression of which was specific to either normal or LDGL NK cells. Together with sophisticated statistical methods, gene expression profiling of a background-matched NK cell fraction thus provides us a wealth of information for the LDGL condition.

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Acknowledgements

We thank all patients, healthy volunteers, and physicians who participated in the collection of NK cell depository. We are also grateful to Dr T Miwa for his helpful suggestions.

Author information

Authors and Affiliations

  1. Division of Functional Genomics, Jichi Medical School, Kawachigun, Tochigi, Japan

    Y L Choi, Y Yamashita, R Ohki, K Koinuma, J Ota & H Mano

  2. Division of Hematology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan

    Y L Choi, Y Isobe & K Oshimi

  3. Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

    H Makishima & F Ishida

  4. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    J Ohashi

  5. CREST, JST, Saitama, Japan

    J Ota & H Mano

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  1. Y L Choi
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Corresponding author

Correspondence to H Mano.

Additional information

This work was supported in part by a grant-in-aid for research on the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health, Labor, and Welfare of Japan, by a grant from Mitsubishi Pharma Research Foundation, by a grant from Takeda Science Foundation, and by a grant from Sankyo Foundation of Life Science.

b >Supplementary Information

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

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Choi, Y., Makishima, H., Ohashi, J. et al. DNA microarray analysis of natural killer cell-type lymphoproliferative disease of granular lymphocytes with purified CD3−CD56+ fractions. Leukemia 18, 556–565 (2004). https://doi.org/10.1038/sj.leu.2403261

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  • DOI: https://doi.org/10.1038/sj.leu.2403261

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