title: Role of autocrine and paracrine production of granulocyte-macrophage colony-stimulating factor and interleukin-1 beta in the autonomous growth of acute myeloblastic leukaemia cells--studies using purified CD34-positive cells.
abstract: The blast cells from some patients with acute myeloblastic leukemia (AML) proliferate autonomously in vitro. We have previously identified four groups of AML blasts based upon their growth characteristics in vitro, in particular the degree of autonomous growth. We have now measured the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-1 beta (IL-1 beta) by AML cells with different growth characteristics, using two sensitive enzyme-linked immunosorbent assays. Our results show a correlation between the capacity of AML blasts to produce GM-CSF and IL-1 beta and the ability to grow autonomously in vitro. Blasts from cells with no autonomous growth (n = 5) secreted low or undetectable amounts of GM-CSF and IL-1 beta. Blasts with totally autonomous growth (n = 10) secreted the highest levels of GM-CSF (mean 2469 pg/10(3) cells) and IL-1 beta (mean 3156 pg/10(6) cells). Whereas blasts with partially autonomous growth (n = 9) secreted intermediate levels of GM-CSF (mean 270 pg/10(6) cells) and IL-1 beta (mean 931 pg/10(6) cells). In order to determine whether GM-CSF production was autocrine or the consequence of paracrine secretion by differentiated leukemic cells, we studied the degree of autonomous growth and production of GM-CSF by CD34-positive blasts from eight patients whose unfractionated cells produced GM-CSF. We found that CD34-positive blasts from six of these cases grew autonomously to a degree comparable to that of the unfractionated cells, and that CD34-positive blasts produced GM-CSF either autonomously or in response to recombinant IL-1 beta. Our data suggests that in the majority of cases, CD34-positive blasts are capable of autonomous growth and autocrine GM-CSF production, however this is variably regulated by the paracrine production of IL-1 beta by CD34-negative cells.
authors.affiliation: University Department of Haematology, City Hospital, Nottingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bradbury
authors.forename: S
authors.initials: S
authors.lastname: Rogers
authors.forename: I A
authors.initials: IA
authors.lastname: Reilly
authors.forename: R
authors.initials: R
authors.lastname: Kozlowski
authors.forename: N H
authors.initials: NH
authors.lastname: Russell
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34; D002455:Cell Division; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006706:Homeostasis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000502:physiology; D053583:Interleukin-1beta; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171); D016178:Granulocyte-Macrophage Colony-Stimulating Factor