Bloom s syndrome

Down s syndrome Bloom s syndrome Fanconi s anemia Klinefelter s syndrome Ataxia telangiectasia Langerhans cell histiocytosis Shwachman s syndrome Severe combined... 

The influence of genetics in leukemia is supported by several observations. For example, among identical twins, the occurrence of ALL is associated with a 20% to 25% chance of the disease developing in the other twin within 1 year. In fraternal twins, there is a fourfold increase in the risk of leukemia compared with the normal population. Additionally, leukemia is known to be increased in several chromosomally abnormal populations. Patients with Down s syndrome have a 20 times increased risk of developing leukemia compared with the rest of the population. Patients with Klinefelter s syndrome and Bloom s syndrome also have an increased incidence of leukemias.7... 

Bloom s syndrome is a rare autosomal recessive disease characterized by a high level of spontaneous chromosomal aberrations and sister chromatid exchange (SCE). Bloom s syndrome involves exhibiting numerous clinical features including predisposition to cancer. The importance of oxidative stress in Bloom s syndrome follows from the overproduction of superoxide, an increase in free radical-mediated damaging processes, and SOD induction... 

Whilst cells are normally equipped with extensive DNA repair systems these can sometimes become overwhelmed, or they may be defective for genetic reasons. Patients with genetic defects in their DNA repair systems (e.g. Xeroderma pigmentosum, Fanconi s syndrome, Bloom s syndrome) are predisposed to the development of cancer [132]. 

Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, et al. 1995. The Bloom s syndrome gene product is homologous to RecQ helicases. Cell 83 655-66... 

Karow JK, Chakraverty RK, Hickson ID. 1997. The Bloom s syndrome gene prod-... 

FanconVs syndrome, a lethal aplastic anemia, is also due to defective DNA repair. Cells from alTected persons cannot repair interstrand cross-links or damage induced by x-rays. Two premature aging disorders (Hutchinson-Gilford syndrome and Bloom s syndrome) and several other disorders Cockayne s syndrome and retinoblastoma) are also associated with defects in DNA repair. Cells from patients with some chromosome abnormalities (e.g., Down syndrome) may also show aberrant DNA repair. 

Bloom s syndrome Repair of double-strand breaks by homologous recombination Mild alkylating agents Carcinomas, leukemias, lymphomas Photosensitivity, facial telangiectases, chromosome alterations... 

There are several genetically determined diseases such as xeroderma pigmentosum (XP), Fanconi s anemia. Bloom s syndrome, ataxiatelangiectasia and porokeratosis Mibelli in which individuals have an increased if not an invariable incidence of cancer (291. These diseases are associated with DNA repair defects, thought to be the cause of the cancer sensitivity (291. In the case of a person with XP, the oversensitivity of the skin to ultraviolet light is inherited and the condition leads to skin cancer. 

Bloom s syndrome, the genetic disease resulting from deficiency in BLM helicase, is characterized by a predisposition to malignancy and also immunodeficiency. In individuals affected with Bloom s syndrome, production of immunoglobulin-producing plasma cells and class switch recombination is impaired.BLM helicase actively unwinds G4 Deficient unwinding... 

The RecQ helicases comprise a small, conserved enzyme family which is essential for maintenance of genomic stability in organisms from E. coli to human. " There is only one RecQ family member in E. coli (RecQ), one in S. cerevisiae (Sgsl), one in S. pombe (Rqhl), and five in Homo sapiens. Three human members of the RecQ family are associated with genomic instability and predisposition to malignancies WRN with Werner s syndrome, BLM with Bloom s syndrome, and RTS (or RECQ4) with Rothmund-Thompson syndrome. RecQ helicases are unusual in their ability to unwind G4 DNA, " ... 

Homonuclear cell lines from Fanconi s anemia (Swift and Hirschhorn, 1966) and Bloom s syndrome (Swift and Hirschhorn, 1966 German and Crippa, 1966) show an increased frequency of spontaneous chromosome breaks. Further, the cells from Fanconi patients appear to have a greater susceptibility to infection with SV40 virus (Todaro et al.y 1966). These features, however, have not yet been developed for use in genetic analysis. 

Suhasini AN, Brosh RM Jr. Fanconi anemia and Bloom s syndrome crosstalk through FANCJ-BLM helicase interaction. Trends Genet. 2012 28 7-13. 

We assume a low DNA ligase I activity in LY-S cells and an ADP-ribosylation-mediated activation of ligase II (9-11). Correlation of ligase activity and radiation sensitivity was reported and a ligase defect indicated in 46BR cells (12) and Bloom s syndrome cells (13,14). So, it seems plausible that the hi radiation sensitivity of LY-S cells is related to an impaired ligase function. 

Studies have also been carried out on individuals with defective DNA repair and with chromosome instability syndromes. The baseline SCE frequency was found to be within the normal range in individuals with ataxia-telangiectasia, Fanconi s anemia, and xeroderma pigmentosum, but a greatly increased frequency of SCE appeared in both lymphocytes and cultured bone marrow cells from individuals with Bloom s syndrome. No deviation from the normal limits has been observed in individuals with Down s syndrome or with balanced translocations or unbalanced karyotypes. 

Furthermore, SCEs show no consistent correlation with the occurrence of spontaneous chromosome aberrations in the various human chromosome breakage syndromes. For example, Fanconi s anemia and ataxia-telangiectasia cells show a normal frequency of SCEs, " but Bloom s syndrome cells show up to a 10-fold increase in the frequency of SCEs. The distribution of SCEs among and within cells also does not correspond with that of the chromosomal aberrations in Bloom s syndrome. 

Cells Chinese hamster CHO(SCl), CHO, V79, V79-4, DON, Cl-1, D-6 Syrian hamster BHK mouse 3T3, ME (mouse embryo primary cells) human HPBL (human peripheral blood lymphocytes), NHF (normal human fibroblasts), XP (xeroderma pigmentosum), FA (Fanconi s anemia), BS (Bloom s syndrome) Muntjac. Activation In experiments in which poor metabolizing ability of cells is augmented by an activation system S9 (Ames S-9 Mix), FL (irradiated feeder layer of metabolizing cells). 

R. S. K. Chaganti, S. Schonberg, and J. German, A manyfold increase in sister chromatid exchanges in Bloom s syndrome lymphocytes, Proc. Natl. Acad. Set. U.S.A. 71, 4508-4512... 

Y. Shiraishi, A. I. Freeman, and A. A. Sandberg, Increased sister chromatid exchange in bone marrow and blood cells from Bloom s syndrome, Cytogenet. Cell Genet. 17, 162-173... 

T. M. Schroeder, Sister chromatid exchanges and chromatid interchanges in Bloom s syndrome, Humangenetik 30, 317-323 (1975). 

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