Clonality of hematopoietic cell subpopulations in essential thkombocythemia

D. Cilloni, D. Garau, G. Sammarelli, B. Savoldo, A. Tafailio, G. Saglio, V. Rizzoli, C. Carlo-Stella

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Abstract

Essential thrombocythemU (ET) is a clonal myeloproliferative disorder due to an acquired abnormality of the pluripotent stem cell. Although the lack of cytogenetic or molecular markers has prevented an extensive investigation of the degree of stem cell involvement, a heterogeneous cell target has been hypothesized in this disease. By using the human androgen receptor gene (HUMARA), the clonality status of blood granulocytes, monocytes, B and T lymphocytes as well as marrow tnononuclear cells (MNC), erythroid BFU-E, granulocyte-maciophage CFU-GM and fibroblastoid CFU-F was investigated in patients with ET (n = 10) and reactive thrombocytosis (n = 3). In addition, marrow CD34cells (n = 2) were examined. Monocytes were enriched by plastic'adherence. CD34cells, granulocytes, B and T lymphocytes were enriched by a magnetic activated cell sorting procedure (Miltenyi) using CD34, GDIS, CD 19 and CD3 monoclonal antibodies, respectively. The purity of enriched fractions was always 295%. Marrow BFU-E and CFU-GM were cultured in a standard mcthylcellulose assay. Otic out of 13 patients was not informative, thus confirming the percentage of beterozygosis of the HUMARA gene. Marrow CD34cells, BFU-E and CFU-GM were clonal in all analyzed ET cases. Blood granulocytes and monocytes were clonal in 10/10 and 9/10 ET cases, respectively, whereas they were polyclonal in secondary thrombocytosis. Conversely, ET-derived B and T cells were clonal in 5/5 and 4/5 cases, respectively. Analysis of individual marrow CFU-F revealed a monoclonal pattern in 5/5 ET patients and a polyclonal pattern in all cases with reactive thrombocytosis. In conclusion, our results demonstrate that: (i) ET is a heterogenous disease with different degrees of stem cell involvement; (ii) a pluripotent stem cell capable of myeloid and lymphoid differentiation is targeted by the disease in the majority of ET patients; (iii) a more differentiated stem cell without the capacity to differentiate into T cells seems to be involved in £25% of the patients; (iv) the clonal status of ET-derived CFU-F might reflect the proliferative advantage of an abnormal stromal progenitor cell population and requires further investigation; (v) T lymphocytes should not be used as a polyclonal control cell fraction.

Original languageEnglish
Pages (from-to)793
Number of pages1
JournalExperimental Hematology
Volume26
Issue number8
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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