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)

Werner's syndrome is a relatively rare autosomal recessive disorder characterized by several features generally associated with aging. This syndrome is classified in the group of chromosome instability syndromes and there is an increased incidence of neoplasia. Hematologic malignancies associated with this syndrome are, however, unusual. Herein we report a case of Werner's syndrome with myelodysplastic syndrome, a clonal preleukemic disorder of hemopoietic stem cells. Such an association, to the best of our knowledge, has not been reported in the English literature so far.
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PMID:Myelodysplastic syndrome in a patient with Werner's syndrome. 787 56

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.
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PMID:Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies. 858 May 57

An unusual case of Werner's syndrome with myelodysplastic syndrome (MDS) in a 63-year-old male is reported. He was transferred to our hospital for evaluation of pancytopenia in August 1994. He had surgery for cataracts at age 47. On admission, his weight was 39 kg and his height was 148 cm. He looked pale, had thin limbs, a bird-like face, loss of hair, a hoarse voice, and atrophic skin with ulcers. A complete blood count showed: hemoglobin 8.7 g/dl; platelet count 1.5 x 10(4)/microliters; and white blood cell count 2,900/microliters with 3% blasts. A bone marrow aspiration revealed hypercellularity with 11.8% blasts and trilineage myelodysplasia. A diagnosis of RAEB was made according to the FAB classification. Cytogenetic analysis of the bone marrow cells revealed multiple aberrations such as 44, XY, -3, -5, add (4) (q?31), add(6) (p2?), del(7) (q22), add(10) (q24), del(12) (q?), add(14) (q32), -15, -16, -17, + mar1, +mar2, +mar3. He died of pneumonia on day 11. Although approximately 700 cases (about 300 cases in Japan) of Werner's syndrome have been reported, the occurrence of hematopoietic malignancies in Werner's syndrome is rare, and the literature includes 8 cases of leukemia and 4 cases of MDS.
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PMID:[Myelodysplastic syndrome with multiple chromosome aberrations in a patient with Werner's syndrome]. 882 85

Werner syndrome (WRN) is a rare autosomal recessive disorder, one of the progeroid syndromes, and is characterized by features of premature aging. The incidence of WRN in the Japanese population, 1 in 200,000, is higher than than that in the Caucasian population. The genetic defect of WRN is unknown. But genetic linkage to several markers on the short arm of chromosome 8 has been reported recently. Here, we studied one family with WRN in which an affected individual had a papillary thyroid carcinoma and myelodysplastic syndrome. Using 4 microsatellites closely located to the WRN locus: D8S360, D8S1055, D8S339 and ANK1, we analyzed the genotypes of this patient, her three siblings and her parents, who were first cousins. The mutative haplotype, identified through the generations in pedigree, helps detect a carrier or a presymptomatic patient. The eldest sister inherited two normal haplotypes, but the second sister inherited one mutative haplotype. There was no difference in clinical signs and symptoms between these sisters. when the WRN gene is isolated, it will help us understand the mechanism of aging.
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PMID:[Genetic analysis of Werner syndrome in a family]. 886 43

A 46-year-old man with Werner's syndrome was admitted with epigastralgia and body weight loss. The peripheral blood findings showed anemia, thrombocytosis and eosinophilia. Bone marrow aspiration and biopsy revealed increases in eosinophils and megakaryocytes, myelodysplastic change with 6.6% myeloblast, and myelofibrosis. Chromosomal analysis revealed 46, XY, +der(1;7), -7, del(20). He was diagnosed as having myelodysplastic syndrome with myelofibrosis or essential thrombocythemia. Three months later, pancytopenia appeared with a relative increase of blasts positive for CD41 and negative for myeloperoxidase. He died of respiratory failure due to pneumonia. An autopsy revealed severe myelofibrosis with proliferation of megakaryocytes and blasts. A final diagnosis of acute megakaryoblastic leukemia was made. Werner's syndrome is rare, and it is even more unusual to have the complication of acute leukemia with der (1;7) seen in this case.
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PMID:[Werner's syndrome developing acute megakaryoblastic leukemia with der(1;7)]. 902 58

A 52-year-old woman with diabetes mellitus (DM) complained of weakness of the arms and legs. She was referred to our hospital in November 2002 because of anemia, thyroid tumor and meningioma including DM. She was short in stature, juvenile bilateral cataract, intractable skin ulcers, clavus on the sole of her foot, a bird-like face and high-pitched voice. Typical physical features led to the final diagnosis of Werner's syndrome. Although the myelogram revealed no abnormal findings except erythroid hypoplasia, cytogenetic analysis of bone marrow cells showed deletion of chromosome 20 in 10% of the analyzed cells, which suggested the possibility of that myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) could occur. She had a thyroidectomy because both lobes of the thyroid gland were enlarged and caused hoarseness, In addition, it is common knowledge that the goiter could become malignant. We need to follow her carefully because she might be vulnerable to malignant disease, including leukemia and malignant meningioma.
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PMID:[A case of Werner syndrome with chromosomal abnormality]. 1707 96

Inactivation of the DNA mismatch repair pathway manifests as microsatellite instability, an accumulation of mutations that drives carcinogenesis. Here, we determined whether microsatellite instability in acute myeloid leukemia and myelodysplastic syndrome correlated with chromosomal instability and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity through disruption of DNA repair function. Acute myeloid leukemia cell lines (n=12) and primary cell samples (n=18), and bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients (n=63) were profiled for microsatellite instability using fluorescent fragment polymerase chain reaction. PARP inhibitor sensitivity was performed using cell survival, annexin V staining and cell cycle analysis. Homologous recombination was studied using immunocytochemical analysis. SNP karyotyping was used to study chromosomal instability. RNA silencing, Western blotting and gene expression analysis was used to study the functional consequences of mutations. Acute myeloid leukemia cell lines (4 of 12, 33%) and primary samples (2 of 18, 11%) exhibited microsatellite instability with mono-allelic mutations in CtIP and MRE11. These changes were associated with reduced expression of mismatch repair pathway components, MSH2, MSH6 and MLH1. Both microsatellite instability positive primary acute myeloid leukemia samples and cell lines demonstrated a downregulation of homologous recombination DNA repair conferring marked sensitivity to PARP inhibitors. Similarly, bone marrow mononuclear cells from 11 of 56 (20%) patients with de novo high-risk myelodysplastic syndrome exhibited microsatellite instability. Significantly, all 11 patients with microsatellite instability had cytogenetic abnormalities with 4 of them (36%) possessing a mono-allelic microsatellite mutation in CtIP. Furthermore, 50% reduction in CtIP expression by RNA silencing also down-regulated homologous recombination DNA repair responses conferring PARP inhibitor sensitivity, whilst CtIP differentially regulated the expression of homologous recombination modulating RecQ helicases, WRN and BLM. In conclusion, microsatellite instability dependent mutations in DNA repair genes, CtIP and MRE11 are detected in myeloid malignancies conferring hypersensitivity to PARP inhibitors. Microsatellite instability is significantly correlated with chromosomal instability in myeloid malignancies.
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PMID:Microsatellite instability induced mutations in DNA repair genes CtIP and MRE11 confer hypersensitivity to poly (ADP-ribose) polymerase inhibitors in myeloid malignancies. 2334 4

Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.
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PMID:WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome. 2550 78

Werner syndrome (WS) confers a high risk of the development of neoplasias, including hematological malignancies, and curative treatment for these malignancies is difficult to achieve. A 44-year-old man with myelodysplastic syndrome was admitted to our hospital. He was diagnosed with mutation-proven WS. He underwent cord blood transplantation (CBT) following fludarabine, busulfan, and melphalan administration. A chimerism analysis of his marrow blood on day 62 showed a donor pattern >95%, which confirmed engraftment. The patient lived for 15 months while maintaining remission of MDS without treatment-related toxicity. Our case shows that CBT can be a treatment modality for WS patients with hematological malignancies.
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PMID:Successful Cord Blood Transplantation in a Werner Syndrome Patient with High-risk Myelodysplastic Syndrome. 3014 58