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Thrombopoietin Enhances the Production of Myeloid Cells, but not
Megakaryocytes, in Juvenile Chronic Myelogenous Leukemia
Nobukuni Sawai,
Kenichi Koike,
Tsukasa Higuchi,
Kinya Ogami, and
Megumi Oda
From the Department of Pediatrics, Shinshu University School of
Medicine, Matsumoto; Pharmaceutical Research Laboratory, Kirin Brewery
Co Ltd, Takasaki; and the Department of Pediatrics, Okayama University,
Medical School, Okayama, Japan.
We previously reported the aberrant growth of granulocyte-macrophage
(GM) progenitors induced by a combination of stem cell factor (SCF) and
granulocyte-macrophage colony-stimulating factor (GM-CSF) in juvenile
chronic myelogenous leukemia (JCML). We examined here the effects of
thrombopoietin (TPO) on the proliferation and differentiation of
hematopoietic progenitors in JCML. In serum-deprived single-cell
cultures of normal bone marrow (BM)
CD34+CD38high cells, the addition of TPO to
the culture containing SCF + GM-CSF resulted in an increase in the
number and size of GM colonies. In the JCML cultures, in contrast, the
number of SCF + GM-CSF-dependent GM colonies was not increased by
the addition of TPO. However, the TPO addition caused an enlargement of
GM colonies in cultures from the JCML patients to a significantly
greater extent compared with the normal controls. There was no
difference in the type of the constituent cells of GM colonies with or
without TPO grown by JCML BM cells. A flow cytometric analysis showed
that the c-Mpl expression was found on CD13+ myeloid
cells generated by CD34+CD38high BM cells
from JCML patients, but was at an undetectable level in normal
controls. The addition of TPO to the culture containing SCF or SCF + GM-CSF caused a significant increase in the production of GM
colony-forming cells by JCML CD34+CD38neg/low
population, indicating the stimulatory effects of TPO on JCML primitive
hematopoietic progenitors. Normal BM cells yielded a significant number
of megakaryocytes as well as myeloid cells in response to a combination
of SCF, GM-CSF, and/or TPO. In contrast, megakaryocytic cells
were barely produced by the JCML progenitors. Our results may provide a
fundamental insight that the administration of TPO enhances the
aberrant growth of GM progenitors rather than the recovery of
megakaryocytopoiesis.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4065-4073
© 1998 by The American Society of Hematology.
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