Over‐expression of tumor necrosis factor‐alpha in bone marrow biopsies from patients with myelodysplastic syndromes: relationship to anemia and prognosis

Abstract

TNF-alpha expression and MVD are elevated in MDS and secondary AML. TNF-alpha expression in BM progenitor cells appears to negatively impact erythropoiesis and overall survival in MDS, and may serve as a potential therapeutic target in patients with hypercellular MDS with marked anemia.

Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: A phase I study

“…In contrast to Keith et al, [13] none of the 12 angiogenic transcripts assessed were consistently elevated or consistently decreased in patients with MDS relative to those with AML. In contrast to Stifter et al, [22] we did not observe a correlation between TNF expression and erythroid hematopoiesis (Supporting Information Fig. 1D).…”

Commonly dysregulated genes in murine APL cells

“…These interactions may alter the ability of APL cells to interact normally with stromal support cells in the bone marrow, and could potentially alter normal patterns of cellular egress from the marrow and/or responses to chemotherapy. 43 We identified several additional dysregulated genes that had previously been implicated in AML or cancer pathogenesis. Examples included genes associated with antiapoptotic activities, including the Bcl2 family member, Mcl1, which is normally expressed in early hematopoietic progenitor cells, and downregulated during normal myeloid development.…”

“…40,41 Similarly, the dysregulation of Tnf in murine APL cells may also alter the expression of a number of other target genes. Tnf is sometimes expressed by AML cells, 42,43 and may promote APL development and/or progression by a variety of mechanisms, including the activation of Vcam1. Vcam1, primarily through its interaction with very late antigen 4 (VLA4; ␣4 ␤1 integrin), provides a key signal regulating the interaction of hematopoietic cells with stromal cells in the bone marrow (see Hall and Gibson for a review 44 ).…”

Anti-leukemic activity of Lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

“…40 Similar or as of yet, undefined signaling cascades may lead to the lintuzumab-mediated reduction in cytokine and chemokine production by AML cells. Elevated circulating levels of cytokines and chemokines including IL-6, MCP-1, IL-8 and TNF-α have been reported in AML and MDS patients, 30,31,[41][42][43] and linked to quality-of-life and treatment issues, such as fatigue and poor prognosis. 43,44 Long term exposure to high TNF-α levels is associated with immunosuppression, tumor growth, and cachexia 32,33,45 as a result of TNF-α-induced production of cytokines and chemokines such as MCP-1, RANTES and IL-8.…”