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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic studies indicate that most tumors are clonal (i.e. unicellular in origin) and have karyotypic alterations. These are not consistent, but non-random abnormalities are being increasingly identified by banding techniques, pointing to the sites on human chromosomes where genes important in neoplastic development are located. It is postulated that tumor progression occurs as a result of genetic lability within the neoplastic clone, leading to emergence of increasingly mutant subpopulations (often recognizable cytogenetically) with more malignant properties. In the context of this hypothesis, acute leukemia, chronic leukemia, and preleukemia can be viewed as differing only in the rate at which an abnormal hemic clone is expanding, with progression to a more aggressive phase (e.g. the "blast crisis" of chronic granulocytic leukemia) reflecting emergence of a new predominant subpopulation as the result of an additional genetic change. These concepts, and the cytogenetic data from which they have been derived, may help our understanding of basic tumor biology, and have some practical applications in the diagnosis of human neoplasms.
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PMID:Tumors as clonal proliferation. 10 6

The paper is concerned with general information on this infection with the description of 2 cases. In one of the patients the disease developed suddenly. There was no reason to suppose SAID, an immunosuppressive state of another genesis. A course of disease was very grave with the involvement of many organs and systems, the bone marrow. The hematological picture of disease was of particular interest (infection carriers--atypical mononuclears were detected in the blood). Diagnosis was made only at autopsy. This case was illustrative in view of usual search for bacterial infection in patients with fever and physicians' insufficient knowledge of this infection. In the second patient suffering from CML cytomegaloviral disease was diagnosed during her life-time. Causes of the fever syndrome (whether it was due to tumor progression or infection) were analyzed. The former seemed more probable.
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PMID:[Cytomegalovirus disease (a description of 2 cases and a review of the literature)]. 282 75

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.
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PMID:Cytogenetically unrelated clones in hematological neoplasms. 290 9

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

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

Chronic myelocytic leukemia (CML) is a model system for the study of many aspects of malignant disease. One aspect that correlates with decreasing therapeutic response is tumor progression. This progression is often accompanied by clonal evolution. In those cases where aggressive therapy does not prevent this evolution, the clinical response to therapy usually proves to be poor and of short duration. Investigators are concentrating their efforts in three primary, but not mutually exclusive, areas with respect to the clinical management of CML. These include: an attempt to distinguish patients at risk for early transformation from those who will have a prolonged chronic phase; the cryopreservation of autologous bone marrow or buffy coat early in chronic phase for subsequent use in the accelerated phase and; endeavors to identify early markers for disease progression allowing intervention before an irreversible blast crisis occurs. This report deals with two types of potential prognostic markers of transformation: chromosomal and cell surface characteristics. The appearance of nonrandom abnormal chromosomal patterns has been correlated with myeloblastic transformation by many investigators. However, there has always been a subset of CML patients who do not undergo clonal evolution. Additionally, the type(s) of transformation in CML may vary depending on the cell lineages involved. Unlike myeloblastic transformants, many of our patients who do not exhibit clonal evolution as a concomitance of disease progression develop a lymphoblastic transformation. Cytofluorometric analysis can distinguish small populations of abnormal cells with lymphoblastic characteristics (HLA DR+). Initial data suggests that patients expressing the HLA DR+ in their "normal" peripheral blood cells are at risk of undergoing lymphoblastic transformation. The combined use of clinical, cytogenetic, and cytofluorometric data to predict an impending transformation and to discriminate between myeloblastic and lymphoblastic populations allows clinicians to manage their patients more effectively.
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PMID:Cytogenetics and cell surface marker analysis in chronic myelocytic leukemia. II. Implications for patient management. 347 Jan 34

An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms.
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PMID:Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies. 360 79

Immune status in relation to tumor progression was evaluated in 175 patients with chronic myeloproliferative diseases. 113 of them had chronic myeloid leukemia, 62 chronic subleukemic myelosis. It was established that immunologic reactivity decline correlated with the rate of tumor progression. The degree of immune deficiency should be taken into consideration in selection of patients for immunotherapy.
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PMID:[The degree of severity of immune disorders and factors influencing the results of their correction in patients with chronic myeloproliferative diseases]. 764 85

De novo methylation of CpG islands is a rare event in mammalian cells. It has been observed in the course of developmental processes, such as X chromosome inactivation and genomic imprinting. The methylation of DNA, an important factor in the epigenetic control of gene expression, may also be involved in tumorigenesis. After the t(9;22) chromosomal translocation and generation of the Philadelphia chromosome, the initiating event in chronic myelogenous leukemia (CML), most of the abl coding sequence is fused to the 5' region of the bcr gene. Expression of the hybrid bcr-abl gene is, therefore, regulated by the bcr promoter. In most cases of CML, one of the two abl promoters (Pa) is nested within the bcr-abl transcriptional unit and should be able to transcribe the type Ia 6-kb normal abl mRNA from the Philadelphia chromosome. However, we have found that the 6-kb transcript is present only in CML cell lines containing a normal abl allele and that the apparent inactivation of the nested Pa promoter is associated with allele-specific methylation. Furthermore, we have noticed that the Pa promoter is contained within a CpG island and undergoes progressive de novo methylation in the course of the disease. This is attested to by the fact that DNA samples from CML patients that are methylation-free at the time of diagnosis invariably become methylated in advanced CML. Since tumor progression in CML cannot always be inferred from the clinical presentation, assessment of de novo CpG methylation may prove to be of critical value in management of the disease. It could herald blastic transformation at a stage when bone marrow transplantation, the only potentially curative therapeutic procedure in CML, is still effective.
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PMID:Progressive de novo DNA methylation at the bcr-abl locus in the course of chronic myelogenous leukemia. 793 18

We have investigated the involvement of tumor suppressor genes (p53 and RB1) and dominantly acting oncogenes (Ras family genes) in BCR/ABL positive and negative chronic myeloproliferative disorders (CMPD) at different stages of the disease, including 26 cases of BCR/ABL+ chronic myeloid leukemia (CML) blast crisis, 9 myelosclerosis with myeloid metaplasia, 4 polycythemia vera, 10 essential thrombocythemia, 1 juvenile CML, and 8 BCR/ABL- CML. The presence of mutations in p53 exons 5 through 9, as well as in RB1 exons 10-27 and in N-, K-, H-Ras exons 1 and 2 was tested by the PCR-Single Strand Conformation Polymorphism technique and by PCR-Direct Sequencing. In addition, Southern blot analysis was used to investigate the occurrence of gross rearrangements in the p53 gene as well as loss of heterozygosity at 17p13, the site of p53. Acute phase BCR/ABL-CMPD cases displayed a high frequency of p53 (2/7) and Ras (3/7) lesions, whereas BCR/ABL- CMPD in chronic phase displayed only germline p53 and Ras sequences. Conversely, p53 inactivation was restricted to only 1/26 cases of BCR/ABL+ CML blast crisis. No alterations in the RB1 gene were detected in any of the cases analyzed. These data indicate that p53 inactivation and/or Ras activation might play a role in acute transformation of BCR/ABL- CMPD and that the molecular mechanisms of tumor progression may be different in BCR/ABL+ versus BCR/ABL-CMPD.
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PMID:Molecular mechanisms of tumor progression in chronic myeloproliferative disorders. 815


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