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Interleukin-1 stimulates proliferation of acute myeloblastic leukemia cells by induction of granulocyte-macrophage colony-stimulating factor release
| Content Provider | Scilit |
|---|---|
| Author | Delwel, R. Buitenen, C. Van Salem, M. Bot, F. Gillis, S. Kaushansky, K. Altrock, B. Lowenberg, B. |
| Copyright Year | 1989 |
| Abstract | In this study, we further established the role of interleukin-1 (IL-1) alpha and IL-1 beta as regulators of proliferation of acute myeloid leukemia (AML) cells. IL-1 stimulated tritiated thymidine (3H-TdR) uptake of AML cells in 13 of 28 cases. Cytogenetic analysis confirmed the leukemic clonality of the IL-1-stimulated cells. Most likely, IL-1 exerted these stimulative effects directly on AML blast cells because IL-1 effectively induced 3H-TdR uptake of CD34-positive AML blasts (separated following cell sorting). Furthermore, adherent cell-depleted AML samples of three patients were more effectively stimulated than nondepleted AML fractions. Cluster and colony formation from adherent cell depleted AML samples could also be stimulated with IL-1, ie, in seven of ten cases analyzed. Subsequent experiments indicated that IL-1 stimulation depended on the release of GM-CSF because (1) induction of DNA synthesis of AML cells by IL-1 could be abrogated with antigranulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, (2) conditioned media (CM) prepared from IL-1 stimulated AML blasts (adherent cell depleted) could stimulate the proliferation of purified normal bone marrow progenitors whereas supernatants from nonstimulated AML blasts did not, and (3) GM-CSF was demonstrated in IL-1/AML-CM with a specific radioimmunoassay, while GM-CSF was not detectable in nonstimulated supernatants. In one case of AML showing significant 3H- TdR uptake in the absence of CSFs, this spontaneous DNA synthesis was found to depend on autocrine IL-1 beta release as it could be suppressed with anti-IL-1 beta antibody or anti-GM-CSF. The blockade by anti-IL-1 beta could be overcome by the addition of high concentrations of IL-1 beta as well as GM-CSF. Thus, in this particular case, endogenously produced IL-1 beta had stimulated the release of GM-CSF which resulted in GM-CSF-dependent proliferation. The results indicate that GM-CSF production by AML blasts is often regulated by IL-1 rather than being constitutive. |
| Related Links | https://ashpublications.org/blood/article-pdf/74/2/586/601787/586.pdf |
| Ending Page | 593 |
| Page Count | 8 |
| Starting Page | 586 |
| DOI | 10.1182/blood.v74.2.586.586 |
| Journal | Blood |
| Issue Number | 2 |
| Volume Number | 74 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1989-08-01 |
| Access Restriction | Open |
| Subject Keyword | Hematology Bone Marrow Stimulated Colony Stimulating Stimulating Factor Macrophage Colony Aml Cells Stimulates Proliferation 3h Tdr Uptake Journal: Blood (Vol- 54, Issue- 2) |
| Content Type | Text |
| Resource Type | Article |
