Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells.

Geißler, Klaus; Öhler, Leopold; Födinger, Manuela; Virgolini, Irene; Leimer, M.; Kabrna, Eva; Kollars, Marietta; Skoupy, Sonja; Bohle, Barbara; Rogy, Michael A.; Lechner, Klaus

doi:10.1084/jem.184.4.1377

Cited by 62 publications

(55 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…35 Moreover, in some patients with CMML, high serum value of this cytokine has been documented. 36 It is therefore possible that the mobilizing effects of GM-CSF, which has been shown for monocytes as well as for other myeloid precursors, may play a role by facilitating the egression of monocytes from the marrow and their subsequent localization to the peripheral blood and other tissue.…”

Section: Cytogenetic Resultsmentioning

confidence: 99%

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

et al. 2006

View full text Add to dashboard Cite

The World Health Organization criteria for diagnosing chronic myelomonocytic leukemia (CMML) are largely based on findings observed in the peripheral blood and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy has not been adequately explored. We examined whether bone marrow biopsy supplemented by immunohistochemistry may be helpful in distinguishing CMML from cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia (aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with those observed in six cases of chronic myelogenous leukemia and in three cases of atypical CML. In addition, we examined whether CD34 immunohistochemistry could be useful in separating cases of CMML with less than 10% blasts (type-1) from cases of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute transformation to acute myeloid leukemia (blastsZ20%). The presence of nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was used to highlight abnormal megakaryocytes. Our results demonstrate significant differences between the groups. CD34 analysis allowed separating CMML type-1 from type-2 and the former from CMML in acute transformation. CD123-positive plasmacytoid monocyte nodules were found only in CMML and not in the other two disease groups. Overlap between CMML and the other two groups were observed with CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and monocytes than CD68, but the differences between CMML and chronic myelogenous leukemia or atypical CML were still not significant. Although CD42b immunostaining facilitated the detection of dwarf megakaryocytes often present in CMML, the distinction between those and the small forms seen in chronic myelogenous leukemia was still problematic.

show abstract

Section: Cytogenetic Resultsmentioning

confidence: 99%

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In addition to macrophages, IL-10 inhibits proliferation of other cell types including T cells (30,31) and normal and leukemic myeloid progenitor cells (32)(33)(34)(35). Although in some instances inhibition of autocrine growth factor production by IL-10 has been shown to contribute to its growth-suppressing activity, no evidence of an IL-10-regulated autocrine growth loop was found for J774 cells (6).…”

Section: Ink4amentioning

confidence: 99%

Stat3-Dependent Induction of p19INK4D by IL-10 Contributes to Inhibition of Macrophage Proliferation

O’Farrell

Zindy

Roussel

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

We have previously reported that IL-10 inhibits proliferation of normal bone marrow-derived macrophages and of the monocyte/macrophage cell line J774. Activation of Stat3 was shown to be necessary and sufficient to mediate inhibition of proliferation. To investigate further the mechanism of growth arrest, we examined the effect of IL-10 on expression of cell cycle inhibitors. We found that IL-10 treatment increases expression of the cyclin-dependent kinase inhibitors p19INK4D and p21CIP1 in macrophages. IL-10 cannot induce p19INK4D expression or block proliferation when Stat3 signaling is blocked by a dominant negative Stat3 or a mutant IL-10Rα which does not recruit Stat3 in J774 cells, whereas p21CIP1 induction is not affected. An inducibly active Stat3 (coumermycin-dimerizable Stat3-Gyrase B), which suppresses J774 cell proliferation, also induced p19INK4D expression. Sequencing of the murine p19INK4D promoter revealed two candidate Stat3 binding sites, and IL-10 treatment activated a reporter gene controlled by this promoter. These data suggest that Stat3-dependent induction of p19INK4D mediates inhibition of proliferation. Enforced expression of murine p19INK4D cDNA J774 cells significantly reduced their proliferation. Use of antisense p19INK4D and analysis of p19INK4D-deficient macrophages confirmed that p19INK4D is required for optimal inhibition of proliferation by IL-10, and indicated that additional IL-10 signaling events contribute to this response. These data indicate that Stat3-dependent induction of p19INK4D and Stat3-independent induction of p21CIP1 are important components of the mechanism by which IL-10 blocks proliferation in macrophages.

show abstract

“…1 We originally reported that extensive in vitro formation of colony-forming unit-granulocyte-macrophage (CFU-GM) without exogenous growth factors can be found in a subset of patients with chronic myelomonocytic leukemia (CMML). 4 We demonstrated that this spontaneous myeloid colony formation in CMML is a granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent in vitro phenomenon, 5 and that CMML patients with high spontaneous CFU-GM growth (>100/10 5 PBMNC) have a worse prognosis compared to patients with low CFU-GM growth, suggesting clinical significance of our observation. 6 We have recently demonstrated that high in vitro myeloid colony formation in the absence of exogenous growth factors is highly associated with molecular aberrations in RASopathy genes in CMML patients.…”

mentioning

confidence: 63%