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Overexpression of heat shock protein 60 and the survival of blast in acute myeloid leukemia after induction therapy

Leukemia volume 14, pages 1529–1530 (2000)Cite this article

Many patients with acute myeloid leukemia (AML) who achieved complete remission (CR) relapse with their disease. We have investigated bone marrow aspirates obtained from AML patients using preparations fixed in 95% ethanol solution and stained with Papanicolaou method. We reported that the blasts (cells with a nucleolus/or nucleoli) at diagnosis were classified into blasts with a clear halo around the nucleolus (BCHN) and non-BCHN blasts, and the patients who had BCHNs at the end of the induction therapy invariably relapsed.1 The persisting BCHNs at the end of the induction therapy were similar to those of BCHNs at diagnosis.1 Several investigators reported that an exposure of tumor cells to antitumor drugs selectively induced synthesis of heat shock protein (HSP).2 Induction of HSP correlated with development of a transient state of cross-tolerance to several cytotoxic agents.2 To clarify the role of HSP in the survival of BCHN and blasts (BCHNs + non-BCHNs) after the induction therapy, we compared the levels of antibodies staining for four types of HSPs (27, 60, 70, and 90) in 58 newly diagnosed patients with AML (M1, 12; M2, 24; M3, 4; M4, 10; M5, 5; M6, 3) at diagnosis and those at the end of the induction therapy.

Thirty-seven patients were treated with BHAC-DMP (N4-behenoyl-1-β-D-arabinofuranosyl-cytosine + daunorubicin (DNR) + 6-mercapto- purine + prednisolone), 10 patients were with cytosine arabinoside (Ara-C) + DNR and 11 patients were with Ara-C + Idarubicin. Two patients underwent bone marrow transplantation, and three died of infection. The other patients received consolidation and maintenance therapy. Bone marrow aspirates were directly smeared on glass slides, air-dried, fixed with methanol and stained with Pappenheim method. Papanicolaou-stained smears were prepared by commonly used preparatory techniques.1 Immunocytochemical examination was performed with the DAKO EnVision system (Dakopatts, Glostrup, Denmark) using monoclonal anti-HSP27 (1:200), anti-HSP60 (1:400), anti-HSP70 (1:200) and anti-HSP90 (1:200) antibodies (Stress Gen, Victoria Canada). It was reported that the level of cellular protection correlated positively with the level of expression of HSP.2 BCHNs were, therefore, graded into three groups as follows: double positive (++) cells, strong and diffuse immunoreactivity in approximately 75% or more of cytoplasm; single positive (+) cells, the positively stained cells other than ++ cells; and negative cells.

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Authors and Affiliations

  1. Department of Pathology, Red Cross Hospital, Japan

    I Emura

  2. Division of Internal Medicine Niigata Cancer Center Hospital, Niigata, Japan

    T Chou & Y Imai

  3. Department of Pediatrics, Niigata University School of Medicine, Niigata, Japan

    T Kakihar

  4. Second Department of Pathology, Niigata University School of Medicine, Niigata, Japan

    T Ishiguro & M Naito

  5. Department of Second Internal Medicine, Niigata University School of Medicine, Niigata, Japan

    H Yoshizawa & M Arakawa

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  1. I Emura
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Emura, I., Chou, T., Imai, Y. et al. Overexpression of heat shock protein 60 and the survival of blast in acute myeloid leukemia after induction therapy. Leukemia 14, 1529–1530 (2000). https://doi.org/10.1038/sj.leu.2401857

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