Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homologs to genes residing on human chromosome 3 (HSA 3) map to four mouse chromosomes (MMU) 3, 6, 9, and 16. In the bovine, two syntenic groups that contain HSA 3 homologs, unassigned syntenic groups 10 (U10) and 12 (U12), have been defined. U10 also contains HSA 21 genes, which is similar to the situation seen on MMU 16, whereas U12 apparently contains only HSA 3 homologs. The syntenic arrangement of other HSA 3 homologs in the bovine was investigated by physically mapping five genes through segregation analysis of a bovine-hamster hybrid somatic cell panel. The genes mapped include Friend-murine leukemia virus integration site 3 homolog (FIM3; HSA 3/MMU 3), sucrase-isomaltase (SI) and glutathione peroxidase 1 (GPX1) (HSA 3/MMU ?), murine leukemia viral (v-raf-1) oncogene homolog 1 (RAF1; HSA 3/MMU 6), and ceruloplasmin (CP; HSA 3/MMU 9). FIM3, SI, and CP mapped to bovine syntenic group U10, while RAF1 and GPX1 mapped to U12.
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PMID:Mapping HSA 3 loci in cattle: additional support for the ancestral synteny of HSA 3 and 21. 178 81

A leukemic mouse model was employed to elucidate the separate effect of leukemia and cytotoxic drugs on the jejunal mucosa and its associated digestive enzymes. The mitotic activity, depth of the crypt and villus-crypt quotient were not significantly changed in leukemic mice in comparison to normal mice. The mitotic activity and the depth of the crypt 48 h after 20 mg methotrexate (MTX)/kg were significantly reduced (p less than 0.01) in leukemic mice. Sucrase (p less than 0.001) and maltase (p less than 0.025) activities in the jejunum from leukemic mice were significantly elevated in comparison with non-leukemic controls. In both non-leukemic and leukemic mice, the dose-response curves for MTX administration revealed a significant decrease and a nadir in sucrase (p less than 0.001) and maltase (p less than 0.0025) activities at the dosage of 20 mg/kg. Thus, in the mouse model, leukemia per se does not contribute to significant diminution in small intestinal function. In the small intestine, MTX appears to be responsible for a decrease in the mitotic activity of crypt cells, depth of the crypt and diminished sucrase and maltase activities.
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PMID:Effect of leukemia and methotrexate on digestive enzymes in the jejunum of mice. 701 77

A comparative map of human chromosome 3 (HSA 3) and pig chromosome 13 (SSC 13) was constructed using physically assigned pig sequence-tagged sites (STSs). Pig STSs representing 11 HSA 3 genes, including v-Raf-1 murine leukemia viral oncogene homolog 1 (RAF1), retinoic acid beta receptor (RARB), cholecystokinin (CCK), pituitary transcription factor 1 (POU1F1), ceruloplasmin (CP), guanine nucleotide binding protein, alpha-inhibiting polypeptide 2 (GNAI2), sucrase-isomaltase (SI), rhodopsin (RHO), dopamine receptor D3 (DRD3), growth-associated protein 43 (GAP43), and somatostatin (SST), were developed. Ten pig STSs were regionally mapped using a somatic cell hybrid panel (SCHP) to SSC 13 with 80-100% concordance. Large-insert probes were obtained by screening a pig yeast artificial chromosome (YAC) library with primers for each STS. Several YACs were identified for DRD3, GAP43, POU1F1, RHO, SI, and SST for fluorescence in situ hybridization (FISH) mapping. Single gene and bi-color FISH with each pairwise combination were used to further define the gene order on SSC 13. While these data confirm chromosome painting results showing that HSA 3 probes hybridize to a major portion of SSC 13, they also demonstrate extensive gene-order differences between man and pig within this large conserved synteny group. Interestingly, several conserved chromosomal regions have been detected between pig and mouse that are not conserved between man and mouse, suggesting that the SSC 13 gene arrangement may be the closest to that of the ancestral eutherian chromosome.
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PMID:Human chromosome 3 and pig chromosome 13 show complete synteny conservation but extensive gene-order differences. 1044 17

Next-generation sequencing techniques have emerged as powerful tools for the understanding of cancer genomes. In recent years, whole-exome and whole-genome sequencing strategies have enabled the annotation of a comprehensive mutation landscape of chronic lymphocytic leukemia (CLL), the most frequent leukemia in western countries. Several recurrently mutated genes have been identified, with a subset being validated as neoplastic drivers. Still, a main challenge remains for the differentiation between driver and passenger mutations among candidates as well as for the functional description of the newly discovered leukemogenic genes that could be utilized for personalized anti-tumor strategies. In this scenario, we have identified the metabolic enzyme sucrase-isomaltase (SI) as one of the most frequently mutated genes in a cohort of 105 CLL patients. Here, we demonstrate that these SI mutations result in loss of enzyme function by preventing the biosynthesis of catalytically competent SI at the cell surface. Transcriptome analyses of RNA from CLL patients with SI loss-of-function mutations have uncovered gene expression patterns that depict ample metabolic reprogramming, pinpointing SI as a putative player in the cancer-associated metabolic switch. These results highlight SI as a relevant target for clinical evaluation in future CLL studies.
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PMID:Functional analysis of sucrase-isomaltase mutations from chronic lymphocytic leukemia patients. 2341 5