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Cyclic Platelet and Leukocyte Count Oscillation in Chronic Myelocytic Leukemia Regulated by the Negative Feedback of Transforming Growth Factor β

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Abstract

We report a case of chronic myelocytic leukemia (CML) with cyclic oscillation of platelet and leukocyte counts and attempt to elucidate the oscillatory mechanism from the standpoint of cytokine regulation of hematopoiesis. A 57-year-old woman with a diagnosis of CML exhibited platelet and white blood cell (WBC) count fluctuations of a cyclic nature. The average duration of the cycles was about 8 weeks. The patient suffered from headache, fatigue, and malaise at the peak of the cycle. The peak thrombopoietin concentration in peripheral blood coincided with a period of decrease in platelet numbers. The change in transforming growth factor β (TGF-β) level paralleled that of the platelet numbers. A progenitor cell assay revealed the suppression of trilineage colony formation in the presence of plasma from the blood cell peak point, and this suppression was completely blocked when the plasma was incubated with an anti-TGF-β antibody. From these findings, we concluded that the cyclic oscillation of the platelet, WBC, and reticulocyte counts had been induced by excess negative feedback to megakaryopoiesis by TGF-β.

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References

  1. Kennedy BJ. Cyclic leukocyte oscillations in chronic myelogenous leukemia during hydroxyurea therapy.Blood. 1970;35:751–760.

    PubMed  CAS  Google Scholar 

  2. Gatti RA, Robinson WA, Deinard AS, et al. Cyclic leukocytosis in chronic myelogenous leukemia: new perspectives on pathogenesis and therapy.Blood. 1973;41:771–782.

    PubMed  CAS  Google Scholar 

  3. Morley AA, Baikie AG, Galton DA. Cyclic leukocytosis as evidence for retention of normal homeostatic control in chronic granulocytic leukemia.Lancet. 1967;2:1320–1323.

    Article  CAS  PubMed  Google Scholar 

  4. Vodopick H, Rupp EM, Edwards L, Goswitz FA, Beauchamp JJ. Spontaneous cyclic leukocytosis and thrombocytosis in chronic granulocytic leukemia.N Engl J Med. 1972;286:284–290.

    Article  CAS  PubMed  Google Scholar 

  5. Sakamaki S, Hirayama Y, Matsunaga T, et al. Transforming growth factor-β1 (TGF-β1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-β receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-β itself with high specificity.Blood. 1999;94:1961–1970.

    CAS  PubMed  Google Scholar 

  6. Hirayama Y, Sakamaki S, Matsunaga T, et al. Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.Blood. 1998;92:46–52.

    CAS  PubMed  Google Scholar 

  7. Hirayama Y, Kohgo Y, Matsunaga T, Ohi S, Sakamaki S, Niitsu Y. Cytokine mRNA expression of bone marrow stromal cells from patients with aplastic anaemia and myelodysplastic sryndrome.Brit J Haematol. 1993;85:676–683.

    Article  CAS  Google Scholar 

  8. Ishibashi T, Miller SL, Burstein SA. Type β transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro.Blood. 1987;69:1737–1741.

    PubMed  CAS  Google Scholar 

  9. Cashman JD, Eaves CJ, Sarris AH, Eaves AC. MCP-1, not MIP-1α, is the endogeneous chemokine that cooperates with TGF-β inhibit the cycling of primitive normal but not leukemic (CML) progenitors in long-term human marrow cultures.Blood. 1998;92:2338–2344.

    PubMed  CAS  Google Scholar 

  10. Carlino JA, Higley HR, Creson JR, Avis PD, Ogawa Y, Ellingsworth LR. Transforming growth factor beta systemically modulates granuloid, erythroid, lymphoid, and thrombocytic cells in mice.Exp Hematol. 1992;20:943–950.

    PubMed  CAS  Google Scholar 

  11. Letterio JJ, Geiser AG, Kulkarni AB, et al. Autoimmunity associated with TGF-β1-deficiency in mice is dependent on MHC class II antigen expression.J Clin Invest. 1996;98:2109–2119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Yasuo Hirayama.

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Hirayama, Y., Sakamaki, S., Tsuji, Y. et al. Cyclic Platelet and Leukocyte Count Oscillation in Chronic Myelocytic Leukemia Regulated by the Negative Feedback of Transforming Growth Factor β. Int J Hematol 77, 71–74 (2003). https://doi.org/10.1007/BF02982605

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  • DOI: https://doi.org/10.1007/BF02982605

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