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)

The use of intensive chemotherapy in the treatment of myelodysplastic syndromes (MDS) has met with some disappointment, although subgroups of patients have been identified in which the response approaches that of de novo acute myeloid leukaemia (AML). We hypothesized that it is not the FAB classification per se, but the biological behaviour of the blasts as shown by their rate of accumulation that influences the response. We have, therefore, included AML with trilineage dysplasia (AML/TLD) as it represents one extreme of the evolution of MDS to AML. We have analysed the results of intensive chemotherapy in 22 patients (median age 60 years; range 26-77 years) with MDS (14) and AML/TLD (8). Response to treatment was analysed by age, interval from diagnosis to treatment, the number of cytopenias, bone marrow blasts and karyotype. Patients were also divided according to the rate of disease progression, shown by the time from diagnosis to treatment (group A = < 3 months; group B = > 3 months). The overall response rate was 87%; 13 (60%) complete responses (CR) and 6 (27%) partial responses. The rate of disease progression was identified as the most significant predictive factor of achieving CR (p = 0.003) (group A 10/12; group B 3/10). Patients presenting with more than 20% blasts also had a better response (p = 0.031). The combined response rates, however, did not differ significantly between the two groups (group A 92%; group B 80%) as 50% of group B achieved a PR. The failure to normalize blood counts was not related to the number of cytopenias before starting treatment. In all cases, PR was associated with persistence of dysplastic morphology and cytogenetic abnormalities. CR was associated with complete morphological and cytogenetic response except in two patients in group B. Dysplastic morphology re-emerged in patients who achieved CR and of these, all but one acquired a new cytogenetic abnormality. Patients in group B who achieved CR all needed two courses compared with a mean of 1.1 for the other group. The median survival from treatment for both groups was 10 months, however, no patient in group B survived more than 20 months. In comparison 33% in group A were alive at 5 years. The rate of accumulation of blasts predicts the response to chemotherapy and the quality of remissions achieved. Patients with rapidly increasing blasts can achieve complete morphological and cytogenetic remissions, although they eventually have a dysplastic relapse. In contrast, intensive chemotherapy for patients with a slow accumulation of blasts may reduce the blast population but with much less benefit on haemopoiesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The rate of disease progression predicts the quality of remissions following intensive chemotherapy for myelodysplastic syndromes. 796 5

De novo acute myeloid leukemia (AML) with dysplastic features in erythroblasts, granulocytes and megakaryocytes, similar to those in myelodysplastic syndrome (MDS) has been described as AML with trilineage dysplasia (AML-TLD) since 1987. Several reports have suggested that AML-TLD is a subtype of de novo AML in adults and has a poor clinical outcome when treated by conventional chemotherapy. It is not certain whether allogeneic bone marrow transplantation (BMT) brings a favorable outcome for AML-TLD. To evaluate the therapeutic efficacy of allogeneic BMT for AML-TLD, we investigated the clinical data and outcomes of conventional chemotherapy and allogeneic BMT for 118 patients with de novo AML. These patients were registered consecutively for the Japan Adult Leukemia Study Group (JALSG) protocols at our institutes. We treated 28 AML-TLD patients and 90 AML-nonTLD patients with conventional chemotherapeutic protocols. AML-TLD patients did not have a significantly different complete remission (CR) rate (75.0% and 88.4% P = 0.1234), but had a significantly higher relapse rate than AML-nonTLD patients (94.1% and 49.3%, P= 0.0007). The outcome of chemotherapy for AML-TLD was significantly worse than that for AML-nonTLD. The overall survival (OS) and leukemia-free survival (LFS) at 6 years were 9.4% and 0% in AML-TLD group, and 51.9% (P= 0.0017) and 46.3% (P< 0.0001) in AML-nonTLD group, respectively. Meanwhile, among the patients who underwent allogeneic BMT, five of eight AML-TLD patients and eight of 14 AML-nonTLD patients were alive, and three and five patients survived more than 3 years, respectively. These results suggest that allogeneic BMT can improve the outcome for AML-TLD, which is poor when conventional chemotherapy is given alone. Allogeneic BMT before relapse may be the best therapeutic strategy for AML-TLD patients under 50 years of age if a donor is available.
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PMID:Allogeneic bone marrow transplantation improves the outcome of de novo AML with trilineage dysplasia (AML-TLD). 1106 20

A novel human leukaemia cell line, designated TMD7, was established from blast cells of a patient with de novo acute myeloblastic leukaemia with trilineage myelodysplasia (AML/TLD). As seen in the original blast cells, TMD7 cells expressed CD7, CD13, CD33 and CD34 and showed an abnormal karyotype containing -5, -7, -8, der(16)t(10;16)(q22;q13). The cells proliferated without added growth factors. Growth was stimulated with the addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and interleukin 3. Differentiation was not observed with the addition of various cytokines. As a cell line derived from AML/TLD has not been reported, TMD7 will be a useful tool as a model of AML/TLD cells. Recently, it was reported that the Notch system has crucial roles to regulate the self-renewal and differentiation of haematopoietic stem cells. We found that TMD7 cells expressed Notch-1 and Notch-2 mRNA. The exposure to recombinant Delta-1 protein, which was one of the Notch ligands, significantly stimulated the growth of TMD7 cells. This is the first human cell line which was shown to proliferate in response to Delta-1, without artificially expressed Notch protein. Therefore, TMD7 will also be a useful tool to study the mechanism of the Notch-Notch ligand interaction.
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PMID:A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein. 1197 20