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ABSTRACT: Background: Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Design and Methods: Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 x 109/L) to determine any correlation to markers associated with immune pathophysiology and outcome. Results: Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels ≥320 pg/mL had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% versus 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% versus 65.5%), a higher response rate to immunosuppressive therapy (84.2% versus 14.3%), and a better 5-years progression-free survival rate (94.1% versus 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% versus 44.4% for refractory cytopenia with multilineage dysplasia). Conclusions: Increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could therefore represent a reliable marker for a benign subset of myelodysplastic syndrome.
Haematologica 02/2013; · 6.42 Impact Factor
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ABSTRACT: Mutation of the PIG-A gene in hematopoietic stem cells (HSCs) results in the loss of glycosylphosphatidylinositol-anchored proteins (GPI-APs) on HSCs, but minimally affects their development, and thus can be used as a clonal maker of HSCs. We analyzed GPI-APs expression on six major lineage cells in a total of 574 patients with bone marrow (BM) failure in which microenvironment itself is thought to be unaffected, including aplastic anemia (AA) or myelodysplastic syndrome (MDS). GPI-APs-deficient (GPI-APs(-) ) cells were detected in 250 patients. Whereas the GPI-APs(-) cells were seen in all six lineages in a majority of patients who had higher proportion (≧3%) of GPI-APs(-) cells, they were detected in only limited lineages in 92.9% of cases in the lower proportion (<3%) group. In all 250 cases, the same lineages of GPI-APs(-) cells were detected even after 6-18 month intervals, indicating that the GPI-APs(-) cells reflect hematopioesis maintained by a self-renewing HSC in most of cases. The frequency of clones with limited lineages seen in mild cases of AA was similar to that in severe cases, and clones with limited lineages were seen even in two health volunteer cases. These results strongly suggest most individual HSCs produce only restricted lineages even in a steady state. While this restriction could reflect heterogeneity in the developmental potential of HSCs, we propose an alternative model in which the BM microenvironment is mosaic in supporting commitment of progenitors towards distinct lineages. Our computer simulation based on this model successfully recapitulated the observed clinical data.
Stem Cells 01/2013; · 7.78 Impact Factor
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ABSTRACT: To characterize bone marrow failure with del(13q), we reviewed clinical records of 22 bone marrow failure patients possessing del(13q) alone or del(13q) plus other abnormalities. All del(13q) patients were diagnosed with myelodysplastic syndrome-unclassified due to the absence of apparent dysplasia. Elevated glycosylphosphatidylinositol-anchored protein-deficient blood cell percentages were detected in all 16 with del(13q) alone and three of six (50%) patients with del(13q) plus other abnormalities. All 14 patients with del(13q) alone and two of five (40%) patients with del(13q) plus other abnormalities responded to immunosuppressive therapy with 10-year overall survival rates of 83% and 67%, respectively. Only two patients who had abnormalities in addition to the del(13q) abnormality developed acute myeloid leukemia. Given that myelodysplastic syndrome-unclassified with del(13q) is a benign bone marrow failure subset characterized by good response to immunosuppressive therapy and a high prevalence of increased glycosylphosphatidylinositol-anchored protein-deficient cells, del(13q) should not be considered an intermediate-risk chromosomal abnormality.
Haematologica 06/2012; · 6.42 Impact Factor
