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Growth characteristics of circulating hematopoietic progenitor cells from
patients with essential thrombocythemia
EM Mazur, JL Cohen and L Bogart
Department of Medicine, Miriam Hospital, Providence, RI 02906.
Peripheral blood mononuclear cells from five patients with essential
thrombocythemia (ET) were cultured in vitro to evaluate restricted
megakaryocytic (CFU-Meg), myeloid (CFU-GM), and erythroid (BFU-E)
progenitor cell development. Varying concentrations of aplastic canine
serum served as the source of megakaryocyte colony-stimulating activity,
and cultured megakaryocyte ploidy distributions were determined by Feulgen
staining and microfluorometry. Megakaryocyte colony growth was strikingly
abnormal in all five patients evaluated. Four of the 5 had a marked
expansion in the concentration of circulating CFU-Meg and 3 of 4 manifested
abnormalities in cultured megakaryocyte colony size (2 unusually large and
1 small). Unstimulated megakaryocyte colony growth was substantially
increased in three patients. However, the fraction of megakaryocyte
progenitors in cell cycle was near or below normal in all instances.
Endomitotic megakaryocyte development was disordered in each of the four ET
patients in whom it was evaluable. In normal subjects, mean megakaryocyte
ploidy values vary biphasically with aplastic canine serum concentration
and peak at 13.2 N following 12 to 15 days of culture. In contrast, day 12
mean ploidy values in cultures from the ET patients remained low at all
aplastic canine serum concentrations and reached a maximum averaging only
8.4 N. Three patients were evaluated serially at extended culture durations
of up to 21 days. The cultured megakaryocyte ploidy was unchanged during
this interval for two of the patients. For the third patient, ploidy
increased steadily, reaching abnormally high ploidy values by day 21.
Progenitor cell expansion was limited to the megakaryocyte line in three
patients. However, two patients had substantial increases in CFU-GM, one of
whom also had a marked increase in BFU-E. There was no significant
unstimulated colony growth by either CFU-GM or BFU-E. These data indicate
that ET is usually characterized by an expansion in the concentration of
circulating CFU-Meg in vivo which manifest both disordered replication and
endoreduplication in vitro.
Volume 71,
Issue 6,
pp. 1544-1550,
06/01/1988
Copyright © 1988 by The American Society of Hematology
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