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

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia

“…[28][29][30] Previously, we have reported overexpression of TNF-␣ and IFN-␥ in the bone marrow of MDS patients. 11 Raza et al 4,21 also observed an increase of TNF-␣, TGF-␤ and IL-1␤ in the bone marrow of MDS. Sato et al 31 have reported that IFN-␥,TNF-␣ and FasL can mediate potent inhibitory signals in hematopoietic cells.…”

“…It is possible that the release of regulatory cytokines such as TNF-␣, IFN-␥, TGF-␤, or others by bone marrow stromal cells, 11 results in the upregulation of not only Fas, but also FasL in hematopoietic cells. Alternatively, MDS bone marrow cells in the process of their evolution, may spontaneously upregulate Fas, FasL or both, or show increased responsiveness to exogenous cytokines thereby facilitating upregulation.…”

“…10 Furthermore, bone marrow macrophages express tumor necrosis factor (TNF)␣ and interferon (IFN)-␥ which have an accelerating effect on apoptosis. 11 Regarding the induction of apoptosis, two factors are known to bind to receptors, induce apoptosis and kill the cells within hours. 12,13 One of them is TNF-␣ and the other is Fas ligand (FasL).…”

Tumor necrosis factor-alpha expressed constitutively in erythroid cells or induced by erythropoietin has negative and stimulatory roles in normal erythropoiesis and erythroleukemia

“…30,41,42 TNF-␣ inhibition of erythropoiesis has been demonstrated in normal hematopoietic progenitors, 43,44 and TNF-␣ expression and suppression of erythropoiesis has been associated with a number of hematopoietic disorders such as Fanconi anemia, 45 myelodysplastic disease, 46 aplastic anemia, 47 and anemia due to chronic disease. 32,48,49 The finding that HCD57 cells could not only express and secrete TNF-␣ in response to EPO, but also respond to TNF-␣ with enhanced proliferation is therefore intriguing.…”

Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL)

“…Resistance against chemotherapy might result from the resistance to apoptosis-inducing drugs such as steroids and Ara-C [5,6]. Regarding the complicated mechanisms that regulate apoptosis in the bone marrow of acute leukemias and myelodysplastic syndromes (MDS), we previously showed that a variety of apoptosis-related molecules are active in hematopoietic cells [7][8][9][10][11][12][13]. However, the associated parameters and molecules involved in apoptosis in AMLL are unclear.…”