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

• Published in: European journal of haematology 2005-12, Vol.75 (6), p.485-491
• Main Authors: Stifter, Gerald, Heiss, Simone, Gastl, Günther, Tzankov, Alexandar, Stauder, Reinhard
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers, Tumor - biosynthesis; Biopsy - methods; Bone Marrow - blood supply; Bone Marrow - metabolism; Bone Marrow - pathology; Case-Control Studies; Disease-Free Survival; Erythroid Precursor Cells - metabolism; Erythroid Precursor Cells - pathology; Erythropoiesis; Female; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - pathology; Male; Microcirculation - metabolism; Microcirculation - pathology; microvessel density; Middle Aged; myelodysplastic syndromes; Myelodysplastic Syndromes - complications; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - pathology; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Predictive Value of Tests; trephine bone marrow biopsy; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2005.00551.x

:  Objectives: An excessive intramedullar progenitor cell apoptosis, to which elevated expression of tumor necrosis factor‐alpha (TNF‐α) might contribute, is considered the main cause of inefficient hematopoiesis in myelodysplastic syndromes (MDS). Enhanced bone marrow (BM) angiogenesis is regarded as an essential cofactor in the progression of MDS to acute myelogenous leukemia (AML) and microvessel formation may be induced by TNF‐α as well. To investigate TNF‐α signaling and neoangiogenesis as potential molecular pathways for therapeutic intervention in MDS with respect to the various MDS subtypes, we performed a morphological and clinico‐pathological study on a large series of paraffin‐embedded trephine BM biopsies. Methods: TNF‐α expression and BM vessels were immunohistochemically analyzed on 89 paraffin‐embedded BM biopsies from patients with MDS and secondary AML, including 12 control samples. Data were correlated with clinico‐pathological and laboratory parameters and analyzed for their prognostic significance considering overall survival. Results: TNF‐α was over‐expressed in MDS patients, especially in those with refractory anemia and its expression correlated with BM cellularity and with magnitude of anemia as well as with microvessel density (MVD). TNF‐α over‐expression was associated with premature deaths. MVD was increased in MDS and secondary AML and correlated with marrow cellularity and expression of TNF‐α, but was not of prognostic significance. Conclusions: TNF‐α expression and MVD are elevated in MDS and secondary AML. TNF‐α 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.