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I Murohashi, S Tohda, T Suzuki, K Nagata, Y Yamashita and N Nara
First Department of Internal Medicine, Tokyo Medical and Dental University,
Japan.
Autocrine growth mechanisms of leukemic blast progenitors in acute
myeloblastic leukemia (AML) were investigated. Colony formation of leukemic
blast progenitors was observed in 14 of 14 patients tested when purified
blast cell fraction depleted of both T cells and monocytes was plated in
methylcellulose without any colony-stimulating factor (CSF). However, there
existed a minimal cell density required to initiate blast progenitor growth
with marked patient-to-patient variation. To clarify the role of cell
density on the spontaneous growth of blast progenitors, we tested whether
leukemic cells produced and secreted some stimulatory humoral factor(s).
Production of colony- stimulating activity (CSA) by blast cells was
observed in 17 of 18 patients tested. Following further depletion of
monocytes, the CSA levels decreased markedly in 14 patients, indicating
that blast cells with monocytoid differentiation were responsible for CSA
production. We also confirmed granulocyte colony-stimulating factor (G-CSF)
and/or granulocyte macrophage-colony-stimulating factor (GM-CSF) production
by leukemic blasts using specific immunologic assays. When leukemic cells
were divided into nonadherent nonphagocytic cell fraction and adherent cell
fraction, only nonadherent nonphagocytic cells showed clonogenecity and
adherent blast cells lacked the colony-forming capacity. The results
indicate that there are at least two blast cell subpopulations in AML: one
is proliferating subpopulation with self- renewal capacity and the other is
supporting subpopulation with functions such as CSF production. The quite
intimate relationship between these two blast cell subpopulations in AML
may play an important role on the growth of leukemic blast progenitors in
vitro.
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