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Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells

Oncogene volume 20, pages 8249–8257 (2001)Cite this article

Abstract

Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML.

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Acknowledgements

We are grateful to A Iida and J-K Yee for the kind gifts of tTAER cDNA and the tetO fragment, and T. Kitamura for the pMX vector. This work was supported in part by a Grant-in-Aid for Research on the Second-Term Comprehensive 10-Year Strategy for Cancer Societies from the Ministry of Health and Welfare of Japan, by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, and Culture of Japan, and by the Science Research Promotion Fund of the Promotion and Mutual Aid Corporation for Private Schools of Japan. J Ota is a research resident of the Japan Health Sciences Foundation.

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Authors and Affiliations

  1. Division of Functional Genomics, Jichi Medical School, Kawachi-gun, Tochigi, 329-0498, Japan

    Ken Ohmine, Jun Ota, Masuzu Ueda, Shu-ichi Ueno, Koji Yoshida, Yoshihiro Yamashita & Hiroyuki Mano

  2. Division of Hematology, Jichi Medical School, Kawachi-gun, Tochigi, 329-0498, Japan

    Ken Ohmine, Masuzu Ueda, Keita Kirito, Norio Komatsu & Keiya Ozawa

  3. Division of Cardiology, Jichi Medical School, Kawachi-gun, Tochigi, 329-0498, Japan

    Shu-ichi Ueno

  4. Department of Hematology, University of Tsukuba School of Medicine, Tsukuba, Ibaraki, 305-8575, Japan

    Shigehiko Imagawa

  5. Department of Hematology, Dokkyo University School of Medicine, Mibu, Tochigi, 321-0293, Japan

    Yuichi Nakamura, Kenji Saito & Kinuko Mitani

  6. Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan

    Miyuki Akutsu & Yasuhiko Kano

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  1. Ken Ohmine
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Correspondence to Hiroyuki Mano.

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Ohmine, K., Ota, J., Ueda, M. et al. Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells. Oncogene 20, 8249–8257 (2001). https://doi.org/10.1038/sj.onc.1205029

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