MDS‐macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones

Abstract

We studied the effect of myelodysplastic syndrome (MDS)-derived adherent cells on colony formation of granulocyte-macrophage progenitors (CFU-GM) in both normal and MDS bone marrow cells. MDS-adherent cells suppressed the growth of normal CFU-GM colony formation. Antibodies against ferritin almost totally neutralized the haematopoietic inhibitory activity. Antibody against gamma-interferon (gamma-IFN) did not have such effect. By cytogenetic analysis using G-staining method, MDS-derived CFU-GM colony showed abnormal clones. MDS have been recognized to be a mosaic of normal and abnormal clones. MDS-macrophages suppressed the growth of progenitor cells derived from normal clones by soluble factors, but did not suppress the growth of those from abnormal clones. It is suggested that progenitor cells derived from abnormal clones are freed from the negative myelopoietic regulator that may be related to the progress of leukaemia.

Reduced expression of inducible gelatinase B/matrix metalloproteinase-9 in monocytes from patients with myelodysplastic syndrome: correlation of inducible levels with the percentage of cytogenetically marked cells and with marrow cellularity

“…The presence of an abnormal monocyte population makes it reasonable to speculate that the altered ME function observed with MDS marrows [50][51][52] may be the consequence of inappropriate modulation of stromal function by MDS-derived monocytes. This speculation is supported by the observation that stromal cells harvested from MDS marrow are not derived from the malignant clone 53 and are presumably intrinsically normal.…”

Distinctive contact between CD34+ hematopoietic progenitors and CXCL12+ CD271+ mesenchymal stromal cells in benign and myelodysplastic bone marrow

“…10 MSCs from MDS and AML patients are abnormal, demonstrating structural chromosomal abnormalities that differ from that of the hematopoietic clone and show distinct genomic profiles in cytogenetically defined or poor prognosis subgroups. [11][12][13][14][15][16][17][18] Despite this, MSCs from MDS patients are capable of supporting hematopoiesis. Recently, perturbation of mesenchymal cell populations was shown to be sufficient to induce MDS in a murine model.…”

Beyond the Niche: Myelodysplastic Syndrome Topobiology in the Laboratory and in the Clinic

“…Altered cytokine expression by MDS marrow-derived macrophages has more uniform support in the literature, including TNFα [ 75 , 80 , 83 ] and, in a subset of patients, IFNγ [ 80 ]. The number of monocyte/macrophages has also been reported to correlate with increased levels of TGFβ in MDS bone marrow biopsies [ 84 ].…”

“…The number of monocyte/macrophages has also been reported to correlate with increased levels of TGFβ in MDS bone marrow biopsies [ 84 ]. Conditioned media from MDS-derived macrophages inhibited the growth of myeloid progenitors (colony forming unit-granulocyte macrophage/CFU-GM) [ 83 ]. MDS patients also have aberrant iron handling and a propensity to iron overload that may alter macrophage function.…”