Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes

Overexpression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ by bone marrow cells from patients with myelodysplastic syndromes

“…37 Further, immunohistochemical staining has revealed that many bone marrow cells were positively stained with anti-TNF-␣ antibody in MDS cases. 4,38 Although these findings were not direct evidence of TNF-␣ production in vivo, they are consistent with the results presented here.…”

Comment on ‘Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes’ by S Tauro et al

“…The latter hypothesis is at least plausible given the recent studies of the IL-3-dependent cell line TF-1 on LS801, an SV-40 transformed MDS stromal cell line: 4 in these co-cultures, death of TF-1 cells by apoptosis was observed despite optimal levels of IL-3 within cultures, suggesting the presence of mechanisms that can override pro-survival signals and induce cell death. A role for TNF-␣ in the pathogenesis of MDS has previously been suggested, 5 and despite the lack of diffusible TNF-␣ in F-36P MDS stromal co-cultures in our studies, a role for this cytokine in inducing apoptosis in F-36P cells cannot be excluded without quantifying levels within the adherent layers. Furthermore, it remains possible that stromal induction of apoptosis in MDS might be mediated by alternative, or hitherto unidentified cytokines.…”

“…The difficulties in establishing stromal layers from bone marrow aspirate mononuclear cells (BMMNC) of MDS patients acknowledged by many workers in the field have restricted investigations on the role of stroma in MDS to a handful studies. [1][2][3][4] It appears that the ability to form stromal layers in vitro may vary from patient to patient, 3,5 with a sizeable number of patients retaining the ability to form normal grade stroma. 1 Albeit inconsistent in type, most MDS stromal layers in vitro may demonstrate some hitherto incompletely characterized phenotypic and/or metabolic defects.…”

Granulocyte colony-stimulating factor inhibits Fas-triggered apoptosis in bone marrow cells isolated from patients with refractory anemia with ringed sideroblasts

“…21,22 Finally, expression of apoptosis-related oncoproteins such as Bcl-2, Bcl-X L and c-Myc is altered in MDS. 23,24 Caspases (cysteine proteases that cleave after aspartic acid) are a group of proteases that are expressed as inactive proenzymes in the cells and are activated by cleavage upon apoptosis induction.…”