Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes

Geißler, Klaus; Hinterberger, W; Jäger, Ulrich; Bettelheim, Peter; Neumann, E; Haas, Oskar A.; Ambros, Peter F.; Chott, Andreas; Radaszkiewicz, Thaddäus; Lechner, Klaus

doi:10.1007/bf00320634

Cited by 21 publications

(15 citation statements)

References 17 publications

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“…The findings of this report are in accordance with the in vitro short-term culture data in MDS marrow, where a very low plating efficiency is the rule 29 and could signify a defective maintenance of hematopoietic progenitors in MDS marrow, which is contributing to the marrow failure. We have also found that by adding a combination of hematopoietic growth factors, a significant increase in the plating efficiency of MDS marrow and blood progenitors can be achieved, presumably by an anti-apoptotic mechanism (manuscript in preparation).…”

Section: Tunel Technique In Separated Cd34supporting

confidence: 80%

Apoptosis in patients with myelodysplastic syndromes: differential involvement of marrow cells in ‘good’ versus ‘poor’ prognosis patients and correlation with apoptosis-related genes

et al. 1999

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Apoptosis has been implicated in the pathogenesis of marrow failure in MDS and the coexistence of marrow hypercellularity along with blood cytopenias was seen as evidence of extreme cell death of mainly mature cells in the marrow (ineffective hematopoiesis). We investigated apoptosis in 53 patients with MDS, by using single-step DNA extraction and gel electrophoresis and then by separating fresh marrow mononuclear cells in CD34+ and CD34 − populations and in situ single cell evaluation of the process. We also studied the expression of apoptosis-related genes, in total and separated mononuclear marrow cells and correlated the findings with clinical and laboratory characteristics. Patients with apoptosis had increased marrow cellularity, longer overall survival and a longer period for transformation to AML. In 'good' prognosis MDS patients, total mononuclear marrow cells, as well as isolated populations of CD34+ and CD34 − cells showed significant degrees of apoptosis; in 'poor' prognosis cases, however, apoptosis was evident only in a large percentage of CD34 + marrow cells and not in total or CD34 − cells. Absence of expression of both c-myc and p53 in total marrow cells was associated with significant degrees of apoptosis and in isolated CD34+ and CD34 − marrow cells the phenomenon was inversely correlated with the level of bcl-2 expression. In conclusion, marrow apoptosis is detected in both CD34+ and CD34 − cells in early MDS and seems to be restricted to CD34+ cells in advanced MDS cases.

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Section: Tunel Technique In Separated Cd34supporting

confidence: 80%

Apoptosis in patients with myelodysplastic syndromes: differential involvement of marrow cells in ‘good’ versus ‘poor’ prognosis patients and correlation with apoptosis-related genes

et al. 1999

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“…Although not routinely available at all centers, these progenitor cell assays can provide a sensitive screening parameter for undiagnosed cytopenias (Tennant, Jacobs et al 1986; Valent 2012). In MDS specifically, they may also have prognostic significance in that low growth suggests a poorer prognosis (Geissler, Hinterberger et al 1988; Shih, Chiu et al 1991). Since 2007 we have been performing these BFUE assays in diagnostically challenging (often 2 nd opinion) cases with the hopes of gaining additional insight into better diagnosis of bone marrow failure states.…”

mentioning

confidence: 99%

Burst-forming unit–erythroid assays to distinguish cellular bone marrow failure disorders

DeZern

McDevitt

et al. 2013

Experimental Hematology

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Patients with cytopenias and a cellular bone marrow can be a diagnostic and a therapeutic challenge. Previous reports have suggested a role for progenitor assays as a potentially useful test for diagnosis and predicting response to therapy. Here we report the results of BFU-E assays in 48 consultative cases of single or multi-lineage cytopenias with cellular marrows. The final diagnoses included 17 patients with myelodysplastic syndrome (MDS); 9 patients with pure red cell aplasia (PRCA) [non-large granular lymphocytosis (LGL) in etiology]; 15 patients with LGL (8 of which had a single lineage cytopenia only while the other 7 had multi-lineage cytopenias); and 7 patients with cytopenias associated with systemic inflammation related to autoimmune conditions. In this cohort, nonmalignant diseases were well-distinguished from MDS by BFU-E growth. Our data suggest that low BFU-E growth (less than 10 BFU-E /105 marrow mononuclear cells) helps to exclude LGL, PRCA, or cytopenias associated with systemic inflammation as a cause of pancytopenia with a sensitivity of 96.8%, specificity of 76.5% and a predictive value of 88.2% (p=0.0001). BFU-E growth was also examined to predict response to treatment. Of the 29 patients in this cohort treated with immunosuppressive therapy across all disease groups, there was an 86% response rate with 25 responders (11 PRs and 14 CRs) and 4 non-responders. This did correlate with higher BFU-E growth. Our results suggest BFU-E assays are a useful adjunct in the diagnosis and management of cytopenias in the setting of a normocellular or hypercellular bone marrows.

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“…A decreased number of CFUs is confirmatory (but not specific) for the diagnosis MDS [15][16][17]. On the other hand, however, a normal CFU count does not role out the diagnosis of MDS.…”

Section: Pathogenesis Classification and Treatment Of Myelodysplastmentioning

confidence: 86%

Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS)

Valent

Wimazal

Schwarzinger

et al. 2003

Wien Klin Wochenschr

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Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid disorders characterized by morphologic dysplasia in one or more cell lineages. Dysplasia in MDS is associated with insufficient production of blood cells and consecutive cytopenia(s). The natural course and prognosis of MDS vary among patients and depend on genetic defects that occur during clonal evolution. In a significant group of patients (roughly 30%) progression to secondary leukemia is observed. These patients appear to have a grave prognosis. The treatment of patients with MDS has to be adjusted to the individual situation and age in each case. In many patients, control of blast cell production by palliative cytoreduction, continuous support with red blood cells, as well as other supportive measures, seem appropriate. In other patients, however, curative therapy (chemotherapy, stem cell transplantation) should be considered. The final decision to offer curative therapy must be based on many different factors including age and the overall situation of the patient. Recently established scoring systems aimed at predicting survival and evolution of leukemia in MDS may be helpful in this regard.

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Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes

Cited by 21 publications

References 17 publications

Apoptosis in patients with myelodysplastic syndromes: differential involvement of marrow cells in ‘good’ versus ‘poor’ prognosis patients and correlation with apoptosis-related genes

Apoptosis in patients with myelodysplastic syndromes: differential involvement of marrow cells in ‘good’ versus ‘poor’ prognosis patients and correlation with apoptosis-related genes

Burst-forming unit–erythroid assays to distinguish cellular bone marrow failure disorders

Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS)

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