Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 15 year old boy with the Fanconi malformation-aplastic anemia syndrome developed erythroleukemia and died of multiple arterial thromboses and hemorrhage. He was one of 10 siblings including 3 affected sisters. He was short of stature and had hypoplastic thumbs; his testes were small and secondary sexual characteristics were inadequately developed. At autopsy he was found to have very few spermatogonia, i.e., a histological picture compatible with the "Sertoli-cell-only" defect. Male hypogonadism in other chromosome breakage syndromes (the Bloom syndrome and ataxia telangiectasia) may have a similar pathogenesis.
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PMID:Studies of malformation syndromes of man XLVII: disappearance of spermatogonia in the Fanconi anemia syndrome. 26 84

The frequent translocation of the c-myc oncogene into the immunoglobulin loci in tumors of B lymphocytes prompted us to ask whether or not disease-associated chromosomal translocations specific for other disorders in different cell types would also involve regions of the genome encoding important differentiation-specific products made by these cells. We have studied the karyotypes of two patients with erythroleukemia and an established erythroleukemia cell line, K562 (late passages), and find translocations within the chromosomal regions to which the genes that encode alpha and beta globin have been assigned. Additionally, we have analyzed the karyotype of cloned B-lymphocytes, including both kappa and lambda producing cells, from a patient with ataxia telangiectasia (AT) and find a translocation between the regions encoding immunoglobulin (Ig) light and heavy chain genes whereas a different translocation not involving these regions is seen in T-lymphocytes from the same patient. These examples provide insight into the mechanism of chromosomal translocation in both cancerous and noncancerous conditions and lead to the speculation that genomic activity is a necessary factor in the generation of some chromosomal translocations.
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PMID:Translocations that highlight chromosomal regions of differentiated activity. 386 96

The TCL1 locus on chromosome 14 band q32.1 is frequently involved in the chromosomal translocations and inversions with the T-cell receptor genes observed in several T-cell tumors, including T-prolymphocytic leukemias, acute and chronic leukemias associated with the immunodeficiency syndrome ataxia-telangiectasia, and adult T-cell leukemia. All breakpoints cloned in this area have been mapped to 14q32.1, an area distant approximately 10,000 kb from the immunoglobulin heavy-chain gene locus on chromosome 14q band 32.3. Except for two cases of inversion, no physical linkage of the cloned breakpoints has been reported, nor has a gene been identified in this region. Taking advantage of chromosome-walking techniques and of the P1 phage, we cloned and characterized 450 kb of the germ-line TCL1 locus, starting from the breakpoints of two independent T-cell leukemias. We show that all molecular rearrangements characterized so far map to these clones, indicating not only that this region is the target of chromosomal rearrangements occurring in this area but also that both inversion and translocations occur within a 300-kb region in the T-cell leukemias. In the attempt to identify a candidate oncogene responsible for the malignant transformation, a CpG island centromeric to the inversions and to the translocations has been identified. Two probes near the CpG island have detected sequences conserved among species, as well as two transcripts in the K562 human erythroleukemia cell line. On the basis of these data, a model of activation of the putative TCL1 oncogene is suggested.
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PMID:Chromosome walking on the TCL1 locus involved in T-cell neoplasia. 841 91