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)

Abnormal regional hypermethylation of the calcitonin gene can be detected in up to 95% of patients with acute nonlymphocytic leukemia (ANLL). We used a polymerase chain reaction (PCR) based assay to detect abnormal regional hypermethylation at this locus in patients with primary myelodysplastic syndromes (MDS). Hypermethylation was detected in 13 of 20 patients (65%) with MDS and was detected in nine patients with MDS and normal cytogenetics. There was no correlation between detection of this abnormality and the subtype of MDS. Four of the 13 patients (30%) with abnormal methylation have progressed to ANLL with a median time to progression of 3.5 months. The actuarial median survival of the cohort with abnormal methylation was 17 months, while that of the cohort with normal methylation is not yet reached. These preliminary findings suggest that detection of abnormal methylation at this locus may be useful as a diagnostic tool in MDS. Furthermore, hypermethylation of the calcitonin gene may be a poor prognostic feature that predicts progression to acute leukemia in patients with primary MDS.
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PMID:Abnormal regional hypermethylation of the calcitonin gene in myelodysplastic syndromes. 750 Jun 48

Macrocytosis in the elderly is often caused by abnormalities of haematological stem cell differentiation. In this study, a group of elderly patients was analysed for four molecular and cell biological parameters. The aim of the study was to screen elderly patients with idiopathic macrocytic anaemia or MDS for a set of alterations which are related to haematological dysplasia. The analyses used were: DNA-methylation at the calcitonin A gene 5'-area, NRAS point mutations at codons 12 and 13, in vitro colony formation of peripheral blood progenitor cells and cytogenetics of bone marrow cells. The results show that a significant portion of elderly patients with idiopathic macrocytosis have one or more of the abnormalities analysed. Hypermethylation of the calcitonin A gene 5'-area at the chromosome 11 band p15 is relatively common (7/15). Chromosomal aberrations (3/12) and NRAS oncogene point mutations (0/15) were rare findings. In vitro culture of erythroid progenitor cells was relatively frequently abnormal (7/15). Eight of our nine macrocytic patients who did not fulfill the FAB criteria for MDS had at least one of the alterations studied; this suggests that these patients might represent early phases of a stem cell disorder.
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PMID:Idiopathic macrocytic anaemia in the aged: molecular and cytogenetic findings. 766 57

It is well documented that the calcitonin gene area in the short arm of chromosome 11 is hypermethylated in most acute leukemias as well as in chronic lymphatic leukemia. In contrast, the gene is normally methylated during the chronic phase of the chronic myeloid leukemia but turns hypermethylated as the disease escalates. As the methylation of the calcitonin gene correlates with the disease activity in chronic myeloid leukemia, it seemed worthwhile to study the gene methylation in other premalignant hematologic conditions with a potential to terminate in fulminant acute leukemia. We report here on the calcitonin gene methylation in patients with myelodysplastic syndromes (MDS) using a methylation sensitive restriction enzyme HpaII and standard Southern blotting techniques. Bone marrow aspirates from a total of 26 MDS patients were studied. In 24 of these patients, the calcitonin gene was hypermethylated. There was no correlation between the methylation status and the morphological stage of the disease. All six patients with a blast count < 5% had a hypermethylated gene. Of the 19 patients with a blast count > 5%, 17 were hypermethylated only two having normal methylation status of the gene. It appears that the hypermethylation of the calcitonin gene area in the short arm of chromosome 11 may be an early event in the pathogenesis of the myelodysplastic syndromes. The methylation analysis may thus be of value as a diagnostic tool in MDS but an abnormal methylation pattern does not seem to have a direct relation with the degree of blast infiltration.
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PMID:Hypermethylation of the calcitonin gene in the myelodysplastic syndromes. 842 80

In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count.
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PMID:Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. 2129 51