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

Chromosomal translocation within B and T cell malignancies has proven a rich source for proto-oncogenes. The obligate DNA breaks within immunoglobulin (Ig) and T cell receptor (TCR) loci are frequently the sites of recurrent translocations. Burkitt's lymphoma established the paradigm by introducing the myc oncogene from chromosome segment 8q24 into the Ig heavy chain gene locus at 14q32. Molecular cloning of an aberrant Ig rearrangement in follicular lymphoma revealed Bcl-2. Bcl-2 constitutes the first member of a new category of oncogenes: regulators of programmed cell death. Bcl-2 blocks apoptosis and maintains long-term immune responsiveness including B-cell memory. The PRAD1 gene of parathyroid adenomas appears to be the elusive Bcl-1 gene of t(11;14)(q13;q32) bearing lymphomas. It proves to be a novel G1 cyclin. Acute lymphoblastic leukemias (ALL) pre-B phenotype produce a E2A/PBX fusion protein that possesses the leucine zipper of E2A with the homeodomain of PBX. Two molecular forms of the BCR/ABL fusion protein are produced by the Philadelphia chromosome. A deregulated p210 tyrosine kinase is found in chronic myelogenous leukemia, while a p190 form predominates in Ph+ ALL. In contrast, T-cell ALLs introduce a potpourri of genes into their T cell receptor loci. However, a common theme is emerging. These oncogenes (Ttg1, Ttg2, SCL, LylI, H0X11) all belong to classic families of transcription factors, possessing LIM domains, helix-loop-helix motifs, or homeodomains. Provocatively, these transcription factors are normally intended for lineages other than T cells. These genes have widened the horizons of both oncogenesis and normal development.
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PMID:Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. 159 Oct 3

In vitro amplification of genomic or cDNA sequences by polymerase chain reaction (PCR) is one of the most powerful tools in recent molecular biology. More than 10(5) copies of DNA sequence ranging from 50 bp to 7 kb can be synthesized in a couple of hours. Ever since its development, PCR has attracted much attention because this strategy would allow the detection of minimal residual disease (MRD) at a very low level. The first successful application of this ultra-sensitive technique was the detection of residual tumor cells carrying a 14;18 translocation in follicular lymphoma. The abnormal transcripts caused by 9;22 translocation in chronic myelocytic leukemia (CML) was also exploited for the amplification to detect the MRD. These techniques have successfully shown the detection of one leukemic cell in 100,000 normal cells. Besides leukemic specific sequences caused by chromosome and gene translocations, unique sequences caused by rearrangements in IgH or TCR gamma, delta chain genes have been used as clonal markers for tumor cells. By targetting these sequences for PCR amplification, almost all ALL patients can be analyzed for MRD. The successive measurement of MRD might contribute to improvement of treatments for leukemic patients.
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PMID:[The detection of minimal residual disease in leukemia by in vitro DNA amplification]. 177 67

The Bcl-2 proto-oncogene was discovered at the t(14;18) breakpoint found in most follicular B-cell lymphomas and some diffuse large-cell lymphomas. Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and extending cell survival by blocking programmed cell death. We examined Bcl-2 protein expression in 82 hematologic malignancies and reactive lymphoid processes. All lymphomas with Bcl-2 rearrangement demonstrated high levels of Bcl-2 protein. However, most follicular and diffuse lymphomas without Bcl-2 rearrangement also displayed intense Bcl-2 staining. In these cases, mechanisms other than classic translocation may be deregulation Bcl-2. The pattern of Bcl-2 staining in follicular lymphoma is the inverse of the pattern in reactive hyperplasia, confirming a role for Bcl-2 immunolocalization in routine diagnosis. Small lymphocytic malignancies, including small lymphocytic lymphoma, mantle zone lymphoma, and chronic lymphocytic leukemia, expressed intermediate levels of Bcl-2. Bcl-2 protein varied in plasma cell dyscrasias. Bcl-2 protein levels in T-cell lymphomas reflected their corresponding stage of development. No substantial Bcl-2 was present in the Reed-Sternberg cells of nodular sclerosing Hodgkin's disease. Chronic myelogenous leukemia was strongly positive for Bcl-2, consistent with the presence of Bcl-2 in normal myeloid progenitors. Immunohistochemistry identified an expanded spectrum of hematopoietic neoplasms in which Bcl-2 may provide a cell survival advantage.
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PMID:Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. 186 40

Usefulness of DNA analysis in diagnosis of hematopoietic malignancy was discussed. Examination on the presence of rearrangement in immunoglobulin (Ig) and T cell receptor (TCR) was the first DNA analysis used for clinical diagnosis of lymphoid malignancy to determine the cell-lineage and clonality of proliferating lymphoid cells. One point mutation in ras oncogene has also been used to detect residual leukemic cells as well as diagnosis of the early relapse of leukemia, although not all leukemic cells have this mutation. Presence of BCR-abl fused gene is a genetic marker for Ph1 chromosome. Analysis of BCR-abl gene has made it possible to diagnose the Ph1 ALL and masked Ph1 CML. Development of PCR technique markedly increased the possibility for the use of DNA analysis in clinical medicine. In addition to Ph1 chromosome, various chromosomal abnormalities resulted in a reciprocal translocation between Ig or TCR gene and other genes in various lymphoid malignancies, such as Burkitt lymphoma and follicular lymphoma. These translocations can be analyzed by Southern hybridization and used for clinical diagnosis.
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PMID:[DNA diagnosis of human cancers: lymphoid malignancies and leukemia]. 198

Using a database comprising 13,266 cytogenetically abnormal neoplasms, the geographic heterogeneity of neoplasia-associated chromosomal abnormalities was investigated by comparing the frequencies of characteristic aberrations in consecutive series of patients with the same diagnosis. Significant frequency differences between geographic areas were found for the aberrations +8, i(17q), +19, and an additional Ph1 chromosome in chronic myeloid leukemia (CML); -5, 5q-, and +8 in acute nonlymphocytic leukemia (ANLL); t(8;21) in ANLL-M2; t(15;17) in ANLL-M3; 5q- and -7 in myelodysplastic syndromes (MDS); t(9;22) and +21 in acute lymphocytic leukemia (ALL); t(14;18) in follicular lymphoma; -8 and -22/22q- in meningioma; and structural abnormalities of 12q in pleomorphic adenoma of the salivary glands (PAS). No geographic incidence variation was detected for -7 and +21 in ANLL; +8 in MDS; 6q- and +8 in ALL; +12 in chronic lymphocytic leukemia; 6q- in non-Hodgkin's lymphoma (NHL); t(8;14) in Burkitt's lymphoma; t(11;22) in Ewing's sarcoma; i(12p) in germ cell tumors; 1p- in neuroblastoma; structural abnormalities of 3q, 8q, and 9p in PAS; or 3p- in renal cell carcinoma. Intraregional frequency similarities between cytogenetically identical abnormalities in related tumor types were also analyzed. No significant correlations were found regarding the incidence of 5q- in ANLL and MDS, 6q- in ALL and NHL, -7 in ANLL and MDS, +8 in ANLL and CML, +8 in ANLL and MDS, +8 in ALL and ANLL, or +21 in ALL and ANLL. The findings indicate that some geographic heterogeneity of tumor-associated aberrations exists both in hematologic neoplasms and in solid tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Geographic heterogeneity of neoplasia-associated chromosome aberrations. 195 98

The authors report the case of a 42-year old woman who developed chronic myelocytic leukemia with Philadelphia chromosome followed, 21 months later, by malignant follicular lymphoma with small cleaved cells and giant cells. This case is comparable to the other associations of acute or chronic myelocytic and lymphocytic blood diseases previously published. Several pathogenic theories are reviewed. They involve chemotherapy with alkylating drugs (but the diagnosis is sometimes simultaneous), cellular oncogens or, more probably, a clonal abnormality of the stem cell sequentially or concomitantly expressed in the cells of both lineages; unfortunately, in the absence of Philadelphia chromosome this theory has not yet been demonstrated on lymphoma cells.
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PMID:[Occurrence of non-Hodgkin's lymphoma in chronic myeloid leukemia]. 348 66

Various kinds of nonrandom chromosomal aberrations have been reported in hematopoietic malignancies. Since the 1980s, many translocation-associated oncogenes and several suppressor oncogenes have been identified and applied for the clinical diagnosis of these malignancies. The former is of major, clinical importance for specific diagnosis made on the basis of molecular detection of the chromosomal translocation, the deregulated expression, and the chimeric mRNA of those genes. Both BCL-1 and BCL-2 genes, associated with mantle zone lymphoma and follicular lymphoma, respectively, belong to the representative deregulated oncogenes by juxtaposition with an immunoglobulin gene enhancer as well as an MYC gene in Burkitt's lymphoma. On the other hand, the MLL gene, associated with infant leukemia, acute monocytic leukemia and secondary leukemia, produces chimeric mRNAs between LTG4, 9, and 19 genes as well as the BCR-ABL chimeric gene in chronic myelogenous leukemia. The detection of minimal residual disease (MRD) by either polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR is becoming an essential test during the course of treatment containing bone marrow transplantation, because positive results of the MRD are closely related to poor prognosis and would have great influence on the choice of treatment plans.
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PMID:[Molecular diagnosis of leukemia and lymphoma]. 817 45

This article reviews both the role of signal transduction in human cancer and the recently uncovered molecular mechanisms involved in a large number of human hematologic malignancies. Chronic myelogenous leukemia, follicular lymphoma, and colorectal carcinoma are used as models to illustrate the different, as well as partly convergent, molecular pathways involved in the multistep process of human neoplasias. Examples are also provided as to how unique molecular markers can be used as fast, sensitive, and precise tools for cancer prevention, early diagnosis, and the management of residual disease.
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PMID:Molecular mechanisms of hematologic malignancies. 842 May 72

In recent years many chromosomal translocations involved in leukemia and lymphoma have been defined at the molecular level. In addition to advancing the understanding of pathological mechanisms underlying the transformation process, the cloning and sequencing of the genes altered by the translocations have provided new tools for diagnosis and monitoring of patients. In particular, the polymerase chain reaction (PCR) methodology yields rapid, sensitive and accurate diagnostic and prognostic information. As leukemias carrying certain translocations confer a higher risk of treatment failure, it is important to identify accurately all positive cases in order to give appropriate therapy. An important new initiative in the diagnostical setting and anti-leukemic therapy is the early detection of minimal residual disease (MRD). If MRD, implying an increased risk of relapse, is reliably detected during apparent clinical remission, alternative strategies could be applied early while the malignant cell burden is still minimal. The PCR assays are clearly more sensitive than other methods of MRD detection including morphology, immunophenotyping and cytogenetics; treatment failure is first detectable by PCR followed by cytogenetic relapse and finally clinical disease. PCR assays have been most often used in the MRD analysis of follicular lymphoma with t(14;18), chronic myeloid leukemia and acute lymphoblastic leukemia (ALL) with t(9;22), ALL with t(4;11), and acute myeloid leukemia (AML) with t(8;21) or t(15;17). PCR amplification is applicable to any other translocation provided the translocation is highly associated with the malignancy and the breakpoints are sufficiently clustered; a quickly increasing number of such specific molecular markers are now available for PCR assays. PCR still remains an experimental investigation for the detection of covert disease. However, the clinical relevance of MRD detection should be evaluated separately for each type of leukemia as significant prognostic differences between disease entities were found. This review describes the PCR assays available for the detection of leukemia cells with specific chromosomal translocations and summarizes the experience with the application of PCR techniques in monitoring patients during the course of the disease.
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PMID:Detection of chromosomal translocations in leukemia-lymphoma cells by polymerase chain reaction. 859 Aug 36

The antiviral, antiproliferative and immunomodulating effect of interferon alpha (INF alpha) has led to its widespread use in malignant diseases. In hematology, the clinical effect of INF alpha has been proven empirically for several lymphoid malignancies--hairy cell leukemia, chronic lymphoid leukemia, multiple myeloma, follicular lymphoma--and also for chronic myeloproliferative diseases, particularly chronic myeloid leukemia. However, after 10 years of use, the impact of INF alpha on patient management compared with conventional treatments remains a matter of debate. Interest in cost-containment and the frequency of adverse effects after long-term treatment also raises many questions. A critical analysis of the role of INF alpha in each specific indication is thus required.
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PMID:[Clinical value of interferon-alpha in the treatment of malignant hematologic diseases]. 920 87


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