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

Of 2,143 biopsy proven cancer patients seen at our hospital over a six year period, 4 (0.19%) patients developed active tuberculosis (TB) during anticancer therapy or shortly after its completion. The cancer diagnoses of those patients were non-Hodgkin's lymphoma, breast cancer, chronic myelogenous leukemia, and astrocytoma. Institution of antituberculous therapy was successful in three patients, however, the TB course was rapidly fatal in the fourth patient with non-Hodgkin's lymphoma despite therapy. The association between TB and neoplasia is emphasized. TB complicating malignant disorders represents complex problem regarding its early recognition and its managements.
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PMID:Tuberculosis in patients with malignant disease. 259 98

Chronic myelogenous leukemia (CML) is an example of a "well-differentiated" neoplasm that develops following neoplastic transformation of a precursor cell. The biology of astrocytic neoplasms can be interpreted in light of concepts that have emerged from studies of the myeloproliferative disorders. Astrocytomas may arise from a pluripotential precursor cell whose progeny, although transformed, retain the ability to differentiate, and do so along astrocytic lines. The result is a neoplasm composed of "mature" tumor cells, similar one to another, and resembling normal astrocytes. Malignant change, like blast crisis in CML, then occurs as a consequence of further molecular genetic events leading to accelerated growth and maturation arrest in a previously differentiating neoplastic cell. This hypothesis challenges the conventional view that astrocytomas arise from astrocytes and that malignant change occurs as a result of dedifferentiation. Extensions of this hypothesis may be relevant to the biology of other glial tumors.
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PMID:The biology of astrocytoma: lessons learned from chronic myelogenous leukemia--hypothesis. 347 24

RAS mutations can be detected in a variable number of patients with myeloproliferative disorders such as myelodysplastic syndromes and acute myeloid leukemia, but are rare events in chronic myelogenous leukemia in chronic phase. However, there is good evidence supporting the involvement of RAS signalling pathway in CML and this could be due to alterations in RAS activity regulatory proteins. The neurofibromatosis (NF1) gene down-regulates the RAS signal transduction pathway through the inhibitory function of its GAP-related domain (GRD) on RAS protein. The loss or alteration of neurofibromin (the NF1 protein) may produce a disfunction similar to point mutations in the RAS gene resulting in the permanent stimulation of the RAS signal transduction pathway. Mutations involving the GRD region of the NF1 gene (GRD-NF1) have been described in a variety of tumors such as colon carcinoma and astrocytoma. Germline mutations and deletions in the NF1 gene, as seen in neurofibromatosis type 1, are also associated with certain myeloid disorders. In the present work, we sought to identify mutations in the codons 12/13 and 61 of RAS gene and in the Lys-1423 codon of GRD-NF1, which are well known hot spots in these genes, in a group of 36 adults and ten children with chronic myelogenous leukemia in chronic phase and blast crisis. Using the PCR-SSCP and the allele-specific restriction assay (ASRA) techniques, we were not able to observe any RAS or NF1 detectable mutation. These findings suggest that RAS and GRD-NF1 mutations are not involved either in chronic phase or in the progression to blast crisis in chronic myelogenous leukemia in adults and children.
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PMID:Mutational analysis of N-RAS and GAP-related domain of the neurofibromatosis type 1 gene in chronic myelogenous leukemia. 978 2

The PARK2 gene, previously identified as a mutated target in patients with autosomal recessive juvenile parkinsonism (ARJP), has recently been found to be a candidate tumor suppressor gene in ovarian, breast, lung and hepatocellular carcinoma that maps to the third common fragile site (CFS) FRA6E. PARK2 is linked to a novel described PACRG gene by a bidirectional promoter containing a defined CpG island in its common promoter region. We have studied the role of promoter hypermethylation in the regulation of PARK2 and PACRG expression in different tumor cell lines and primary patient samples. Abnormal methylation of the common promoter of PARK2 and PACRG was observed in 26% of patients with acute lymphoblastic leukemia and 20% of patients with chronic myelogenous leukemia (CML) in lymphoid blast crisis, but not in ovarian, breast, lung, neuroblastoma, astrocytoma or colon cancer cells. Abnormal methylation resulted in downregulation of PARK2 and PACRG gene expression, while demethylation of ALL cells resulted in demethylation of the promoter and upregulation of PARK2 and PACRG expression. By FISH, we demonstrated that a lack of PARK2 and PACRG expression was due to biallelic hypermethylation and not to deletion of either PARK2 or PACRG in ALL. In conclusion, our results demonstrate for the first time that the candidate tumor suppressor genes PARK2 and PACRG are epigenetically regulated in human leukemia, suggesting that abnormal methylation and regulation of PARK2 and PACRG may play a role in the pathogenesis and development of this hematological neoplasm.
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PMID:Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia. 1628 63

Astrocytomas are central nervous system neoplasms, which are derived predominately from astrocytes. On the basis of the histopathologic characteristics astrocytomas are graded from I to IV. The cells that demonstrate the greatest degree of anaplasia are used to determine the histologic grade of the tumor. The mean age of survival are approximately 10 years from the time of diagnosis for pilocystic astrocytomas (World Health Organization grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2 to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV). The treatment is a combination of surgery, radiation, and chemotherapy depending of the grade of astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of his chronic myelogenous leukemia treatment failing to show recurrence of the astrocytoma 10 years after standard treatment for astrocytoma.
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PMID:Regression of grade III astrocytoma during the treatment of CML with imatinib mesylate. 1698 42

We report here a 4-month-old child with a large, solid enhancing mass involving predominantly the suprasellar and diencephalic regions, with extension of both hemispheres. The patient underwent partial resection of the mass by right temporal craniotomy. Histological diagnosis was of a low-grade glioma consistent with pilomyxoid astrocytoma. Cytogenetic analyses revealed an insertion on chromosome 17 that involved disruption of the BCR gene. This finding suggests a possible rearrangement of this gene that could act in a similar way to chronic myeloid leukemia with formation of a chimeric tyrosine kinase protein. This study may suggest the use of inhibitors of tyrosine kinase proteins as an alternative treatment approach in cases of refractory or disseminated pilocytic astrocytomas.
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PMID:BCR gene disruption in a pilomyxoid astrocytoma. 1708 Jul 23

Imatinib mesylate (STI571), an inhibitor of alpha- and beta-platelet-derived growth factor receptors (PDGFR) and other tyrosine kinases, is a well established treatment for chronic myeloid leukaemia and gastrointestinal stromal tumours. Moreover, it is under investigation for the therapy of several other malignant tumours since protein kinases are frequently mutated or otherwise deregulated in human malignancies and they serve as a target for differentiating between tumour cells and normal tissues. The objective of this study was to determine whether gamma radiation could sensitize astrocytoma cell lines to the effects of imatinib in vitro. For this purpose, T98G and MOG-G-UVW astrocytoma cells were treated with imatinib alone or in combination with gamma radiation. The clonogenic survival assays performed with the combination of imatinib with radiation demonstrated that the drug had an additive antiproliferative effect in both cell lines considered. Imatinib confered greater radiosensitivity on the T98G tumour cells effecting a significant decrease in colony formation compared with radiation alone. These data provide a rationale to further investigate the combination of imatinib with radiation, keeping in mind that this may result in unexpected toxicities that are not observed with either treatment alone.
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PMID:Influence of imatinib mesylate on radiosensitivity of astrocytoma cells. 2003 6

PDCD5 (programmed cell death 5) is an apoptosis related gene cloned in 1999 from a human leukemic cell line. PDCD5 protein containing 125 amino acid (aa) residues sharing significant homology to the corresponding proteins of species. Decreased expression of PDCD5 has been found in many human tumors, including breast, gastric cancer, astrocytic glioma, chronic myelogenous leukemia and hepatocellular carcinoma. In recent years, increased number of studies have shown the functions and mechanisms of PDCD5 protein in cancer cells, such as paraptosis, cell cycle and immunoregulation. In the present review, we provide a comprehensive review on the role of PDCD5 in cancer tissues and cells. This review summarizes the recent studies of the roles of PDCD5 in inflammation and cancer. We mainly focus on discoveries related to molecular mechanisms of PDCD5 protein. We also discuss some discrepancies between the current studies. Overall, the current available data will open new perspectives for a better understanding of PDCD5 in cancer.
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PMID:Roles of programmed cell death protein 5 in inflammation and cancer (Review). 2782 15