Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human glucocerebrosidase cDNA clone was isolated from a human chronic myelogenous leukemia (line K562) cDNA library using a 36-nucleotide-long synthetic probe (GC-36). The 2.4-kb cDNA contains 184 bp of 5' nontranslated sequences, the complete coding region, and 546 bp of 3' nontranslated sequences followed by 100 bp of poly(A). A primer extension experiment indicated that the cDNA is at least 51 bp shorter than the mRNA at the 5' end. In normal human placenta as well as in fibroblasts from Gaucher's disease patients, a major mRNA species of 2.6 kb hybridizes with the cDNA probe. The amounts of the glucocerebrosidase mRNA in normal placenta and Gaucher's cells are comparable. The cDNA was linked to the SP6 promoter and transcribed in vitro. The resultant RNA, when translated in a cell-free system, yielded a polypeptide of 55 kD, which is the size expected from the coding sequence. The cDNA was inserted into an SV40 shuttle vector, under the transcription control of the SV40 early promoter. COS-M6 cells were transfected with this construct and the biological activity of the cDNA was assayed by monitoring the increase in glucocerebrosidase activity, using 4-methyl umbiliferyl glucopyranoside as a substrate. There was a two- to three-fold increase in enzymatic activity in the transfected cells, compared to nontransfected cells. These results prove the authenticity of the glucocerebrosidase cDNA and provide the basis for experiments to understand the nature of the genetic alterations responsible for Gaucher's disease.
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PMID:Efficient in vitro and in vivo expression of human glucocerebrosidase cDNA. 243 2

We report the case of a 46-year-old female with coexisting type I Gaucher's disease and chronic myeloid leukemia (CML). The diagnosis of Gaucher's disease was made in early childhood by bone marrow biopsy and was recently confirmed by biochemical demonstration of reduced leukocyte beta-glucocerebrosidase activity and the presence of Gaucher cells in a bone marrow aspirate. We analyzed the patient's genomic DNA for the underlying glucocerebrosidase mutations and have found homozygosity for a C-->T transition in cDNA nucleotide 593 (159 Pro-->Leu), presently an undescribed mutation. After initiation of replacement therapy with alglucerase we observed a significant increase of the platelet count in our patient. The diagnosis of CML was based on standard hematological parameters and the detection of the Philadelphia chromosome (Ph). With intermittent treatment with busulfan the patient has remained in chronic phase for nine years. The patient suffered from hepatosplenomegaly and thrombocytopenia, both of which can be caused by Gaucher's disease and CML. The aggravation of skeletal manifestations of Gaucher's disease, which occurred at the time of diagnosis of CML, could be due to increased production of leukocyte-derived glucocerebrosides that were not appropriately degraded because of the genetic beta-glucocerebrosidase deficiency.
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PMID:Coincidence of Gaucher's disease due to a private mutation and Ph' positive chronic myeloid leukemia. 972 84