Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignancy associated with a poor outcome. Despite the relatively high incidence of MDS in the elderly, differentiation of MDS from de novo acute myeloid leukemia (AML) still remains problematic. Identification of genes expressed in an MDS-specific manner would allow the molecular diagnosis of MDS. Toward this goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like fractions have been collected from a variety of leukemias in a large-scale and long-term genomics project, referred to as "Blast Bank," and transcriptome of these purified blasts from the patients with MDS were then compared with those from AML through the use of oligonucleotide microarrays. A number of genes were shown to be expressed in a disease-specific manner either to MDS or AML. Among the former found was the gene encoding the protein Delta-like (Dlk) that is distantly related to the Delta-Notch family of signaling proteins. Because overexpression of Dlk may play a role in the pathogenesis of MDS, the disease specificity of Dlk expression was tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS. Dlk could be the first candidate molecule to differentiate MDS from AML. The proposal is made that microarray analysis with the Blast Bank samples is an efficient approach to extract transcriptome data of clinical relevance for a wide range of hematologic disorders.
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PMID:Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction. 1143 12

Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.
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PMID:DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia. 1451 49

Myelodysplastic syndrome (MDS) is a clonal disorder of haematopoietic stem cells. Despite the high incidence of MDS in the elderly, effective treatment of individuals in its advanced stages is problematic. DNA microarray analysis is a potentially informative approach to the development of new treatments for MDS. However, a simple comparison of 'transcriptomes' of bone marrow mononuclear cells among individuals at distinct stages of MDS would result in the identification of genes whose expression differences only reflect differences in the proportion of MDS blasts within bone marrow. Such a 'population shift' effect has now been avoided by purification of haematopoietic stem-like cells that are positive for the cell surface marker AC133 from the bone marrow of healthy volunteers and 30 patients at various stages of MDS. Microarray analysis with the AC133+ cells from these individuals resulted in the identification of sets of genes with expression that was specific to either indolent or advanced stages of MDS. The former group of genes included that for PIASy, which catalyses protein modification with the ubiquitin-like molecule SUMO. Induction of PIASy expression in a mouse myeloid cell line induced apoptosis. A loss of PIASy expression may therefore contribute directly to the growth of MDS blasts and stage progression.
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PMID:DNA microarray analysis of stage progression mechanism in myelodysplastic syndrome. 1453 11

We present an update of our results with transplantation of highly purified stem cells from one to three loci mismatched parental donors. Sixty-three pediatric patients with acute lymphoblastic leukemias (n = 32), acute myeloid, chronic myeloid and myelomonocytic leukemias (n = 13), myelodysplastic syndromes (n = 4), lymphomas (n = 4), and various nonmalignant diseases (n = 10) underwent transplantation. Mobilized peripheral-blood stem cells were selected with either anti-CD34- or anti-CD133-coated microbeads. Patients received a median of 19.5 x 10(6) purified cells and <25,000 CD3+ T lymphocytes per kilogram, with no regular posttransplant pharmacological immunosuppression. Engraftment occurred in 98% of patients (primary sustained engraftment, 83%; engraftment after reconditioning/stem cell boosts, 15%). Moreover, all survivors but one had a stable three-lineage engraftment with a median follow up of 4.1 years (range 0.6-8 years). Primary acute graft-versus-host disease (GvHD) grade II was seen in only 7% of patients. No severe primary acute GvHD grades III-IV occurred. Thirteen percent of the patients developed transient chronic GvHD. Probability of disease-free survival (DFS) at 3 years was 60% for patients with nonmalignant diseases and 48% for patients with acute lymphatic leukemia (ALL)/non-Hodgkin lymphoma (NHL) in complete remission (CR)1-3. None of the ALL/NHL patients with active disease survived. Children with acute and chronic myeloid leukemias had a poorer outcome (3-year DFS = 18%), whereas two of four patients with myelodysplastic syndrome (MDS) are alive. Relapse probability of the whole group was not significantly increased when compared to a historical control group. The incidence of lethal viral infections was 18% between 1995 and 2002 and has since been reduced to 8% by the introduction of new therapeutic strategies. In summary, the use of stem cells from haploidentical parental donors should be strongly considered in all children who need transplantation but lack an identical donor.
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PMID:Long-term outcome after haploidentical stem cell transplantation in children. 1552 45

CD45 is a hematopoietic lineage-restricted antigen that is expressed on all hematopoietic cells except for some mature cell types. Cells expressing CD45 and CD34 but lacking CD38 and lineage antigens (CD45+CD34+CD38-Lin- cells) are well-documented hematopoietic stem cells (HSCs), and CD45+CD34-CD38-Lin- cells are probably less mature HSCs. In myelodysplastic syndromes (MDS), the malignant transformation site is a matter of debate, and CD45+CD34+CD38-Lin- HSCs were recently reported to be clonal. In the study reported here, we detected CD45-CD34-CD38-Lin- cells in the peripheral blood and bone marrow of patients with MDS and isolated them by successive application of density centrifugation, magnetic cell sorting, and fluorescence-activated cell sorting. Fluorescence in situ hybridization showed that CD45-CD34-CD38-Lin- cells had the same chromosomal aberration as the myeloblasts. In addition to CD45- and CD34-, they lacked CD117 and CD133 expression. Generally, MDS cells have extremely reduced hematopoietic potential compared with normal hematopoietic cells, but we documented the following in some patients. Freshly isolated CD45-CD34-CD38-Lin- cells did not form any hematopoietic colonies but had long-term culture-initiating cell activity. When cocultured with stroma cells, CD45-CD34-CD38-Lin- cells showed only weak potential for proliferation and differentiation, yet they differentiated into CD34+ cells and then mature myeloid cells. This newly identified cell population represents the most immature immunophenotype so far identified in the hematopoietic lineage and is involved in the malignant clone in MDS.
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PMID:Identification and hematopoietic potential of CD45- clonal cells with very immature phenotype (CD45-CD34-CD38-Lin-) in patients with myelodysplastic syndromes. 1584 69

Fresh frozen bone marrow biopsies were evaluated immunohistochemically, applying monoclonal antibodies against CD31, CD34, VEGFR-2 and CD133, a novel marker identifying human endothelial progenitor cells (EPCs). Specimens of 51 patients diagnosed with MDS were compared with 16 AML and 18 controls. The percentage of CD34 expressing cells was increased and CD31 expression was decreased in advanced stages of MDS compared with normal BM. VEGFR-2 expression was also raised in MDS. Here we show for the first time that increased numbers of CD133 positive cells are present in the majority of MDS patients. Additionally, those cells occasionally seem to contribute to capillary forming units in bone marrow.
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PMID:Increased CD133 expression in bone marrow of myelodysplastic syndromes. 1603 25

Recent data suggest that myeloid neoplasms are organized hierarchically in terms of self-renewal and maturation of early progenitor cells, similar to normal myelopoiesis. In acute myeloid leukemia (AML), the NOD/SCID mouse-repopulating leukemic stem cells usually co-express CD123 with CD34, but lack CD38. So far, however, little is known about expression of other markers and targets on these progenitors. In the present study, expression of target antigens on CD34+/CD38- cells was analysed by multi-color flow cytometry in patients with AML (n = 18), myelodysplastic syndromes (MDS, n = 6), chronic myeloid leukemia (CML, n = 8) and systemic mastocytosis (SM, n = 9). The IL-3Ralpha chain (CD123) was found to be expressed on CD34+/CD38- cells in a majority of the patients in all disease categories. Independent of the type of disease, the vast majority of these stem cells co-expressed aminopeptidase-N (CD13) and CD44 in all patients. By contrast, the CD34+/CD38- progenitor cells expressed variable amounts of the target receptor CD33, c-kit (CD117) and AC133 (CD133). In conclusion, neoplastic stem cells in various myeloid neoplasms appear to express a similar phenotype including target antigens such as CD13, CD33 and CD44. Since many of these targets are not expressed on all stem cells in all patients, the elimination of the entire clone may require combinations of targeted antibodies or use of additional drugs.
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PMID:Detection of molecular targets on the surface of CD34+/CD38-- stem cells in various myeloid malignancies. 1632 50

To explore the relationship between the expression of CD133 and pathogenesis of leukemia and MDS, immunocytochemistry method was used to examine the expression of CD133 in bone marrow cells of patients with leukemia and MDS. The results showed that the positive rate of CD133 in 41 acute leukemia patients was 51.2%. The expression of CD133 in AML patients (16/29, 55.2%) was significantly higher than that in control group (2/15, 13.3%). There was no significant difference in CD133 expression between CML and control group. The positive rate of CD133 in 9 patients with MDS was 55.56% (5/9). There was no significant difference between MDS and normal control. The expression of CD133 in all leukemia cells with CD34(+) was higher than that in leukemia cells with CD34(-), and there was significant difference in expression of CD133 between them (P < 0.05). The expression of CD133 had no relationship with the clinical prognostic factors such as sex, age, the percentage of leukemic cells in peripheral blood and in bone marrow, WBC counts, hemoglobin concentration, platelet counts and LDH level. It is concluded that the expression of CD133 in bone marrow cells of patients with AML is higher than that in control group. The expression of CD133 is significantly correlated with the expression of CD34. The high expression of CD133 may be an adverse prognostic factor in acute leukemia.
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PMID:[Expression of CD133 in bone marrow cells of patients with leukemia and myelodysplastic syndrome]. 1760 47

A new myeloid leukemia cell line (CG-SH) with normal cytogenetics was established from a patient with acute myelogenous leukemia (AML) following myelodysplastic syndrome (MDS). The cells of CG-SH are immature blasts and have an immature myeloid phenotype (positive for myeloperoxidase, CD7, CD34, CD38, CD117, HLA-DR, negative for CD10, CD19, CD20, CD41, CD42). A partial expression of CD13, CD15, CD65 and a weak expression of CD33 and CD133 was noted. The cells are negative for EBER. By molecular analysis, a mutation of NRAS and heterozygous mutations of RUNX1 were detected. No mutations were detected in FLT3-ITD, MLL-PTD or NPM1. By real-time PCR, a series of 19 microRNAs was identified which are strongly expressed in CG-SH. In conclusion, a new cell line was established which will be useful for the study of AML with normal cytogenetics and mutations in NRAS and/or RUNX1.
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PMID:Characterization of a new myeloid leukemia cell line with normal cytogenetics (CG-SH). 1941 91

Myelodysplastic syndrome (MDS) is a kind of clonal stem-cell disorder in which aberration within a hematopoietic stem cell (HSC) gives rise to the entire disease as in acute myeloid leukemia (AML). Studies have showed that contrasting normal stem cells, AML stem cells express CD96 and CD123, but lack of CD90, although both of them reside within the CD34(+)CD38(-) population. So far, little is known about expression of the markers on MDS HSC. In this study, we analyzed the immunophenotypic characteristics of CD34(+)CD38(-) bone marrow (BM) cells by multicolor flow cytometry in 38 patients with MDS and 10 control patients. We found that CD34(+)CD38(-) BM cells coexpressed CD13, CD33, CD117, CD133, and HLA-DR almost in all patients, but in MDS they expressed higher amounts of CD13 (79% +/- 16% vs. 36% +/- 13%, P < 0.05) and CD133 (66% +/- 20% vs. 25% +/- 13%, P < 0.05). CD90 was expressed in all control patients but just in 63% of patients with MDS. No control patients had an expression of CD2, CD5, CD7, CD44, CD96, and CD123, which expressed variable amounts in 17-53% of patients with MDS. The level of CD13 in RCMD (89% +/- 7%), RAEB-1 (88% +/- 11%), and RAEB-2 (81% +/- 13%) were obviously higher than that of RA (63% +/- 16%, P < 0.05). CD2, CD5, and CD7 were more frequently observed in RAEB or INT and HIGH-R cases. Taken together, we demonstrate MDS stem cells display deranged phenotypic abnormalities that may make them particularly difficult to eradicate using therapies targeted against surface antigens, and the percentage of cells expressing CD13 is notably higher in patients with high-grade MDS that may be a potential prognostic indicator of MDS in the future.
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PMID:Detection of molecular targets on the surface of CD34+CD38- bone marrow cells in myelodysplastic syndromes. 2066 87


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