Effects of granulocyte-macrophage colony-stimulating factor and erythropoietin on leukemic erythroid colony formation in human early erythroblastic leukemias

Abstract

Erythroid colonies from five patients with an early erythroblastic leukemia were obtained in “serum-free” cultures in the presence or absence of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and homogeneous native erythropoietin (Epo). Erythroid colonies with abnormal morphology and karyotype could be grown in different culture conditions. Their erythroid nature was ascertained by the presence of carbonic anhydrase I and glycophorin A. Leukemic erythroid progenitors strongly differed from normal progenitors in that spontaneous colonies were always obtained, sometimes with an extremely high plating efficiency (up to 5.7%). Colonies were found to be autonomous from exogenous hematopoietic growth factors because they were still obtained with a high plating efficiency at an average of one cell per culture in the absence of any added growth factor. No evidence for an autocrine secretion of Epo or GM-CSF emerged because Epo or GM- CSF could not be detected by biologic or radioimmunologic assays from the culture supernatant or cellular extracts of the leukemic cells and that Epo or GM-CSF antibodies did not block autonomous growth. In all cases, however, hematopoietic growth factors increased the plating efficiency of the abnormal erythroid progenitors. In the two “de novo” leukemias, leukemic erythroid progenitors responded primarily to Epo, whereas in the three other patients' (chronic myeloid leukemia) blast crisis they responded maximally to GM-CSF plus Epo. Recombinant erythroid-potentiating activity had no effect in any of these cases. These results suggest that the leukemic erythroid clonogenic cells arise from expansion of erythroid progenitors at different levels of differentiation (ie, CFU-E or BFU-E, depending upon the disease) and that autonomous growth is not related to a secretion of Epo or GM-CSF.

Action of interleukin-3 on the proliferation of leukaemic progenitor cells from patients with acute myeloblastic leukaemia

“…Thus, some AML progenitor cell populations which could respond to either IL-3 or GM-CSF can be further stimulated by a different stage-specific growth factor G-CSF but not by IL-3 or GM-CSF, which may work on cells at a similar progenitor level. Similar observations have been reported in some leukaemic cases with respect to GM-CSF and lineagespecific growth factor erythropoietin (Mitjavila et al 1987;Asano et al 1988a). Thus, proliferation of AML progenitor cells may be hierarchically modulated by haematopoietic growth factors.…”

Quantitative expression of erythropoietin receptor (EPO‐R) on acute leukaemia cells: relationships between the amount of EPO‐R and CD phenotypes, in vitro proliferative response, the amount of other cytokine receptors and clinical prognosis

“…EPO is known to enhance the growth of clonogenic leukaemia cells in the presence of granulocyte/macrophage colonystimulating factor, IL3 or phytohaemaglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) in vitro (Mitjavila et al, 1987;Asano et al, 1988;Motoji et al, 1990). On the other hand, gIFN reportedly downregulated the EPO-R of erythroid progenitor cells (Stopka et al, 1998).…”

“…EPO-R expression has been identi®ed in erythroblasts as well as in CD34 cells, tumour cell lines and leukaemia cells from patients (Wollman et al, 1996;Shinjo et al, 1997a;Chiba et al, 1997). EPO normally exerts its effect on early progenitor cells or stem cells (Nakamura et al, 1994), but also enhances the growth of acute myeloid leukaemia (AML) (Mitjavila et al, 1987;Asano et al, 1988;Motoji et al, 1990). However, EPO-R expression and its prognostic implication in leukaemia patients remain to be investigated.…”

Immuno‐ and cytochemical characterization of congenital leukemia: A case report

“…Spontaneous erythroid colony formation seen in our patient is not a common finding in acute leukemias. It has been described in a few cases with erythroleukemia [12], while in myeloproliferative disorders it is a common and well-known phenomenon [3,13].…”