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Abstract

We studied functional disturbances in hemopoietic microenvironment and cytokine production by stromal sublayer in long-term bone marrow cultures and peripheral blood macrophages from patients with various forms of myelodysplastic syndrome. Production of factors stimulating the growth of normal erythroid and granulocytic precursors by cells of the stromal sublayer from patients with refractory sideroblast anemia and refractory anemia with excess blasts is impaired compared to cells from healthy donors. The medium conditioned by macrophages from patients with chronic myelomonocytic leukemia displayed a higher ability to stimulate the growth of granulocytes and macrophages compared to media conditioned by cells from donors and patients with refractory sideroblast anemia and refractory anemia with excess blasts. Cultured stromal cells and macrophages produced tumor necrosis factor-alpha and interleukin-6. Their content in media conditioned by cells from patients with myelodysplastic syndrome surpassed that in healthy donors. Our results suggest that production of cytokines by stromal microenvironmental cells is impaired in patients with various forms of myelodysplastic syndrome.

VCAM-1 Expression on Bone Marrow Stromal Cells from Patients with Myelodysplastic Syndromes

“…The imprints were put on a roentgen fi lm and developed. Several immunoblots (2)(3)(4) were performed for each patient. Albumin served as the control for electrophoresis.…”

“…These fi ndings are consistent with published data and results of our previous experiments, which illustrate dysfunction of the stroma in MDS patients. For example, MDS patients are characterized by a reduced number of fi broblast precursors in the bone marrow [1] and low capacity of the hemopoietic microenvironment to maintain hemopoiesis in long-term cultures [1,2] and monolayer cultures of the bone marrow [6]. Recent cytogenetic studies revealed the presence of chromosomal aberrations in mesenchymal cells from patients with MDS and AL [4,5].…”

“…The bone marrow from patients with myelodysplastic syndromes (MDS) serves as a model for in vitro studies of the stroma. This heterogeneous group of diseases is characterized by clonal injury to the stem hemopoietic cell and high risk for transformation into acute myeloleukemia [9].This diseases manifests in vitro by qualitative and functional changes in the hemopoietic microenvironment [2,3,[11][12][13]. Most studies were conducted on non-fractionated stromal microenvironment, therefore it was diffi cult to characterize abnormalities in individual types of cells.…”

Murine xenogeneic models of myelodysplastic syndrome: An essential role for stroma cells

“…However, Elstner et al showed that marrow from MDS patients formed poor adherent stromal layers [61], which may affect proliferation of MDS precursor cells [62,63]. Also, long-term bone marrow cultures from patients with MDS revealed impaired production of cytokines, such as IL-3 or hepatocyte growth factor [61,62,64–66]. The fact that healthy donor HSC, nevertheless, engraft in the marrow of MDS patients provides support for the concept that alterations in MDS stroma are dependent upon the presence of clonal MDS cells and are reversible upon their elimination.…”