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)

Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century.
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PMID:The malignant primate? 180 19

Retroviruses first attracted attention as the etiological agents of tumors in various animals, including birds, rodents and primates. The retrovirus-induced tumors comprise above all T- and B-cell leukemias/lymphomas, chronic myelogenous leukemia and mammary carcinomas, and are characterized by a long latent period between infection and manifestation of the disease. Since their detection, oncogenic retroviruses have been the object of intense study contributing to our knowledge of basic mechanisms and molecular events involved in carcinogenesis in general. An essential step in the retrovirus life cycle is the covalent integration of the double-stranded DNA copy of viral RNA into the cellular genome, forming the provirus. The proviruses are quite stable and are generally a permanent acquisition for the cellular genome. Therefore, the presence of the provirus can have profound genetic implications for the host cell. There are at least three main routes that are assumed to lead to retroviral oncogenesis: Transduction of cell-derived oncogenes (v-onc) carried by some retroviruses, activation of cellular proto-oncogenes (c-onc) in cis by insertional mutation or activation of cellular genes in trans by virus encoded transcription factors.
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PMID:The significance of retroviruses in oncology. 209 76

We present a case of a 63-year-old man who was diagnosed CML at the onset of bladder transitional carcinoma. He had been treated with subcutaneous injection of natural interferon-alpha at the dose of 2 X 10(6) U on consecutive days. Four weeks later, he achieved remission and then received curative operation. Ph1 chromosome transiently decreased to 40%. For more than 16 months, he remained in remission. Since in CML Ph1 clone can be found in B cells and CML itself may result in hypogammaglobulinemia which may be basis of carcinogenesis, it was speculated that hypogammaglobulinemia found in this case related to carcinogenesis.
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PMID:[Chronic myelogenous leukemia maintained in remission by interferon alpha presenting with bladder cancer]. 281 Jul 96

Within a very short time the application of molecular biology to cancer research has resulted in an essential change and extension of our knowledge of transformation processes and tumor development. For the first time these mechanisms can be understood in a causal manner and causal cancer therapy seems to be possible in the near future. In this manuscript an attempt is made to give a brief survey of the influence of oncogenes on carcinogenesis. An account is given of the origin of viral oncogenes, viral mechanisms of cell transformation and activation of cellular oncogenes. Additionally, kinetics and targets of tumor proteins are discussed. The complexity and diversity of genetic regulation of growth and differentiation is discussed in some well known diseases such as chronic myeloid leukemia, Burkitt lymphoma, retinoblastoma and acute myeloid leukemia.
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PMID:[Oncogenes]. 303 83

Cytogenetic studies are providing clues to the growth regulatory genes involved in human carcinogenesis and to mechanisms that alter their function. Investigations of chromosome translocations in B and T cell lymphomas and in chronic myelogenous leukemia have demonstrated the effects on protooncogenes of transposition within the genome, with or without structural change in the gene. These studies have also provided evidence for many previously unidentified human oncogenes. Similarly, the recognition through cytogenetics of gene amplification units in aggressive forms of certain tumors has helped to define another important type of somatic genetic change in neoplasia, again involving both known and previously unknown oncogenes. The observation of nonrandom chromosomal deletions in other malignancies has contributed to the delineation of an additional major class of tumorigenic genes, called suppressor genes, which appear to have a significant role in inherited malignancies and are now being actively sought in many common cancers. Finally, chromosome studies have helped to demonstrate the clonal nature of most neoplasms and the importance, in tumor progression, of sequential somatic genetic changes within the neoplastic clone. This latter phenomenon appears to depend primarily on acquired genetic lability in the tumor cell population. Karyotypic data are providing leads to its basis, as well as to the significance in carcinogenesis of constitutional chromosomal fragility and of specific fragile sites within the genome of different individuals.
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PMID:Chromosomal approaches to oncogenes and oncogenesis. 305 65

Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.
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PMID:Temporal distributions of risk for radiation-induced cancers. 331 74

Nonrandom patterns of chromosome abnormality in tumors are providing clues to the location of oncogenes and their activation mechanisms. Studies of translocations in Burkitt's lymphoma cells have shown that the c-myc proto-oncogene is consistently juxtaposed with a rearranged and transcriptionally active immunoglobulin gene locus, with resultant myc gene deregulation. In other B cell tumors, translocations appear to bring previously unrecognized oncogenes (bcl-1, bcl-2) into similar association with the immunoglobulin heavy-chain locus. T cell receptor genes may also "activate" known and unknown oncogenes after chromosome translocation. In chronic myelogenous leukemia, the translocated c-abl oncogene forms a "hybrid" gene in its new location on the Philadelphia chromosome, with altered function. Gene amplification units, seen as cytogenetically homogeneous staining regions in chromosomes or as double-minute bodies in metaphases, can represent multiple copies of oncogenes and be important in late stages of tumor progression. Other significant alterations in gene dosage, recognized as gain or loss of all or part of a specific chromosome, also occur in human neoplasms, but their specific role in carcinogenesis is largely undefined.
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PMID:Chromosomal approaches to the molecular basis of neoplasia. 332 6

Recent improvement in the methods of chromosome analysis has allowed recognition of consistent chromosome alterations in several human cancers, especially leukemias and lymphomas. At the same time, newly discovered human cellular oncogenes have been mapped to individual chromosomes, with precise band assignment. Some of the assignments are coincident with the breakpoints of translocations observed in particular tumors. In fact, a relocation of the corresponding oncogenes has been observed in the cells of some of these tumors. Two notable examples are that of the t(9;22) translocation of chronic myelogenous leukemia (CML), causing the transfer of the oncogene c-abl from chromosome 9 to chromosome 22, and that of the t(8;14) translocation of Burkitt lymphoma, causing the transfer of the oncogene c-myc from chromosome 8 to chromosome 14. These findings can be taken as indicative of a critical role of chromosome alterations in the origin of cancer, through the activation of one or more cellular oncogenes, although there is no firm evidence that such an activation actually occurs. In addition, some concern exists over the validity of accepting in vitro transformation of a cell line by oncogenes as a model of carcinogenesis in man. For these reasons the question on the significance of chromosome alterations in leukemias and lymphomas should not be considered entirely settled yet. Useful models, whose study may lead to the clarification of this important point, are represented by premalignant conditions, such as the myeloproliferative disorders, where chromosome abnormalities are present before the development of a bona fide neoplasm, and by the aneuploidy syndromes, in which there exists an association between a constitutional chromosome anomaly and an increased risk of cancer.
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PMID:Some questions on the significance of chromosome alterations in leukemias and lymphomas: a review. 638 40

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3-9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3-9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution.
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PMID:Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia. 794 95


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