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)

Since 1988 the number of growth hormone (GH)-treated patients has markedly increased worldwide. To date, leukemia has been observed in 31 patients during or following GH therapy and related malignancies in 2 further patients. Leukemia occurred in 10 patients in Japan, 10 in the USA, and 10 in Europe, and in 1 patient in Canada. In 29 patients GH therapy had been started in 1975 or later. The onset of leukemia was 1984 or later in 28 patients with a mean time between the start of GH therapy and leukemia onset of 5.0 (0.2-18.8) years. Patients had received both pituitary and recombinant GH in moderate doses. In 15 patients definite additional leukemia risk was evident: Fanconi anemia in 2, myelodysplastic syndrome in 1, Bloom's syndrome in 1, radiation for brain tumor (+chemotherapy) in 9, chemotherapy in 2. The leukemic patients without a strong additional risk do not represent a definitely higher leukemia incidence worldwide, except for Japan where the occurrence is higher than expected.
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PMID:Leukemia in growth-hormone-treated patients: an update, 1992. 129 14

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin-C-induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X-ray-induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid-type aberrations. She had a number of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelodysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin-C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous 'butterfly rash' Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.
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PMID:Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings. 755 65

Bloom syndrome is a genomic instability syndrome associated with predisposition to development of various types of malignancy. In this report, we described a 7-year-old boy with Bloom syndrome (BS) and myelodysplastic syndrome (MDS) associated with monosomy 7 and loss of the Y chromosome. To our knowledge, this was the first case with BS showing monosomy 7 and MDS during the early childhood period.
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PMID:Myelodysplastic syndrome associated with monosomy 7 in a child with Bloom syndrome. 1061 31

Bloom syndrome (BS) predisposes affected individuals to a wide variety of neoplasms including hematological malignancies. Thus far, cytogenetic findings in hematological neoplasms have been reported in only a few BS patients. We present the karyotypic findings in a BS patient diagnosed with acute myeloid leukemia (AML), FAB subtype M1, and a review of the literature, showing the preferential occurrence of total or partial loss of chromosome 7 in BS patients with AML or myelodysplastic syndromes (MDS).
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PMID:Chromosomal aberrations in Bloom syndrome patients with myeloid malignancies. 1145 28

The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.
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PMID:Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests. 1182 67

The newly identified protein BLAP75/RMI1 associates with the helicase BLM and is critical for the function of the homologous recombination complex. Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom's syndrome). We have analyzed the common polymorphism Ser455Asn in RMI1 and its association with cancer risk in acute myeloid leukemia (AML, N=93), myelodysplatic syndromes (MDS, N=74), and malignant melanoma (MM, N=166). Two control groups were used: one population-based (N=119) and one recruited from spouses of cancer patients (N=189). The results showed a consistent pattern, where carriers of the Asn variant had a significantly increased risk of AML/MDS. The risk of AML/MDS for SerAsn+AsnAsn subjects was odds ratio (OR)=1.7, 95% confidence interval (CI) 1.1-2.5 or MM was OR=1.5, 95% CI 1.0-2.2. Age might modify the effect of RMI1 on cancer risk. This was most evident for MM: AsnAsn homozygotes > or =64 years showed OR=2.7, 95% CI 1.1-6.0, whereas individuals <64 years showed OR=0.87, 95% CI 0.31-2.5. These results indicate a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.
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PMID:Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma. 1790 Aug

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

Bloom syndrome is a rare autosomal recessive disease, in which BLM gene is mutated, leading to genome instability and proneness to malignancy. It is characterized by short stature, sun-sensitive rash and immunodeficiency. We present a case of bloom syndrome with myelodysplasia complicated by acute myeloid leukaemia. This case has new ophthalmologic manifestations. We confirmed the diagnosis by detection of high rate of sister chromatid exchange. The patient received chemotherapy but did not tolerate it well and developed fungal pneumonia.
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PMID:Bloom syndrome with myelodysplastic syndrome that was converted into acute myeloid leukaemia, with new ophthalmologic manifestations: the first report from Syria. 3041 Jul 76