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)

DNA methylation has been studied intensively during the past years in order to elucidate its role in the regulation of gene expression, gene imprinting and cancer progression. Earlier studies have shown that a general genomic under-methylation is associated with chronic lymphocytic leukemia and metastatic prostate cancer. Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia. We have now explored possible methylation changes associated with benign and malignant breast tumors. Two approaches were employed: (i) chemical determination of general genomic methylation status and (ii) base-specific analysis of the methylation changes in the promoter of the calcitonin gene with the aid of genomic sequencing. The results did not reveal any changes of total DNA 5-methylcytosine content in ductal carcinoma of breast in comparison with benign tumors. There was a small, yet significant, increase in 5-methylcytosine content in lobular carcinoma. Genomic sequencing of the promoter region of the calcitonin gene, however, revealed a striking hypermethylation at or around the transcription start site of the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this region was either entirely unmethylated or only slightly methylated. The latter changes may reflect a regional hypermethylation of the short arm of chromosome 11, which harbors, in addition to the calcitonin gene, a number of putative or established tumor-suppressor genes. Our results demonstrate that genomic sequencing in its present form can be used for a reliable and precise DNA methylation analysis of primary human tumors.
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PMID:Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing. 898 Feb 49

To investigate the relationship between the abnormal methylation of the calcitonin (CT) gene and the karyotypic abnormality in predicting the disease progress in chronic myeloid leukemia (CML), we studied the abnormal methylation of the CT gene in 47 CML patients by using a sensitive PCR method. At the same time, cytogenetic study was made in the same group of patients. The abnormal methylation of CT gene was found in only 4 of 24 patients in chronic phase, but in 6 of 9 patients in accelerated phase, and in 12 of 14 patients in blast crisis. Sequential studies in one patient also showed that the gene is normally methylated during the chronic phase but turns hypermethylated as the disease progresses. Our findings indicate that abnormal methylation of the 5' region of the CT gene is regularly a marker of disease progression in CML.
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PMID:[The methylation of CT gene in chronic myeloid leukemia]. 1037 99

To investigate the role of calcitonin(CT) gene hypermethylation in the transformation from the initial chronic phase to blast crisis of chronic myeloid leukemia, 31 CML patients were studied by using Hpa II-PCR. The results showed that the 10.52%(2/19) chronic phase, 71.4%(5/7) accelerated phase and 80.0%(4/5) blast crisis of patients had CT gene hypermethylation and that the increased methylation of the CT gene were related with the disease progression. The reports indicated that the hypermethylation of CT gene might be a useful marker for predicting the evolution of CML and selecting chronic phase patients for BMT.
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PMID:[Study of calcitonin gene methylation in chronic myeloid leukemia by using Hpa II-PCR]. 1208 Jun 52

BACKGROUND: The peptide hormone calcitonin (CT) can significantly effect the proliferation rate of CT receptor (CTR) positive human cancer cells. We wish to identify additional human cancers expressing CTRs and assay the effects of CT on their growth rates and signal transduction pathways. RESULTS: The expression of the human calcitonin receptor (hCTR) gene in the chronic myelogenous leukemia cell line K562 was examined. RT-PCR on total RNA extracted from K562 cells detected the presence of hCTR mRNA. Further analysis demonstrated that multiple hCTR isoforms were present. Incubation of K562 cells with salmon calcitonin (sCT), but not amylin, caused an increase in intracellular levels of cAMP similar to that induced by forskolin treatment. We further demonstrated that butyrate induced erythroid differentiation of K562 cells caused a significant decrease in hCTR mRNA levels. However, phorbol myristate acetate (PMA) induced megakaryocytic differentiation of these cells had no significant effect on hCTR mRNA levels. We demonstrated that exposure to various concentrations of sCT had no effect on the cellular proliferation of K562 cells in vitro. CONCLUSION: Chronic myelogenous k562 cells express multiple CTR isoforms. However, CT does not effect K562 proliferation rates. It is likely that the small increase in intracellular levels of cAMP following CT treatment is not sufficient to interfere with cellular growth.
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PMID:Calcitonin receptor gene expression in K562 chronic myelogenous leukemic cells. 1274 9

BACKGROUND Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia. On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement. The patient was diagnosed with hypercalcemia in the context of a CML blast phase. Treatment with hydration, calcitonin, and zoledronic acid lead to control of his symptoms and normalization of his serum calcium levels. After discharged, the patient was maintained on palliative treatment and zoledronic acid management without new episodes of hypercalcemia. However, eight months later, the patient died. CONCLUSIONS Evidence from the literature demonstrates a highly variable clinical presentation of CML-associated hypercalcemia, commonly occurring during an accelerated or a blast phase, and associated with poor survival. Multiple mechanisms could be involved and are not exclusive of each other. Better understanding of the pathophysiologic mechanisms involved in CML-associated hypercalcemia could lead to improvement in clinical and laboratory evaluation of these patients and be the foundation for the development of better management strategies and possibly target-directed therapy to positively improve prognosis.
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PMID:Chronic Myeloid Leukemia Associated Hypercalcemia: A Case Report and Literature Review. 2823 41


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