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)

Tremendous advances in our understanding of acute leukemia have been made through the development of new technologies and close collaboration between immunologists, molecular biologists, and clinical oncologists. These technological advances have included the development of monoclonal antibodies (MoAb) reactive with surface antigens on leukemic cells which can help confirm the lineage and diagnosis of acute leukemia. More importantly, MoAb in conjunction with morphology and cytochemical stains have led to the identification of FAB-MO and the more common recognition of FAB-M7. MoAbs have also helped define prognostic groups, e.g., T-cell leukemia, mature B-cell leukemia, and rare groups such as CD7+ AML. However, the greatest advances in our understanding of acute leukemia has occurred with the application of genetic techniques. Disregulation of genes responsible for normal growth and differentiation initiates the molecular events that lead to the transformation and proliferation of cells recognized clinically as leukemia. Non-random cytogenetic abnormalities apparently contribute to this gene disregulation and specific abnormalities are associated with clinically important subgroups. In acute lymphoblastic leukemia (ALL), the t(9;22), t(1;19), and t(4;11) appear to have a poor prognosis. In acute myeloblastic leukemia (AML), -7/7q-;-5/5q-, 11q23 abnormalities have poor outcomes while t(15;17) and in some series t(9;11), t(8;21), and inv(16) have a good response to therapy. Molecular studies of somatic cell (immunoglobulin and T-cell receptor) gene rearrangements have assisted in the diagnosis and classification of ALL. The application of the polymerase chain reaction technique to specific gene rearrangements has provided a useful approach to minimal residual disease. Specific gene activation (N-myc, evi-1) or fusion genes such as the alpha retinoic acid receptor (alpha RAR) and pml have been identified as the specific cause of some cases of leukemia. The cloning of specific chromosomal breakpoints identified in leukemia (as has been done for CML) will result in specific probes which can be used to make the diagnosis rapidly at the molecular level. Because of the tremendous number of recent developments, this paper will focus only on major developments that will soon have a clinical impact.
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PMID:Pathology and immunology of acute leukemia. 143 16

Diagnosis- and/or prognosis-related alterations of (proto) oncogenes may be detected in neuroblastoma (N-myc), carcinoma of breast and ovary (HER2/neu), NHL (c-myc, bcl-2), CML (c-abl/bcr), and some other neoplasias. A wide variety of methods for the detection of gene alterations can be applied. The methods of detection have to be chosen according to the expected mechanisms of oncogene activation, the availability of adequately prepared tissue, and the technical standard of the laboratory. The sensitivity, specificity, and quantitation of morphological techniques (immunohistochemistry and in situ hybridization) is restricted and their results have to be interpreted most carefully. Whenever possible, at least two different techniques should be used, preferably on two different levels, i.e. RNA/DNA and protein. Furthermore, the combination of morphological and non morphological methods should be aspired.
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PMID:[Oncogenes and oncogene products--possibilities and significance of their detection]. 170 8

To examine whether determination of (1) the copynumber or restriction pattern of certain oncogenes or (2) the mutational activation of the N-ras gene might contribute to the risk classification of acute lymphoblastic leukemia of childhood (ALL), we investigated DNA isolated from lymphoblasts of untreated patients. Restriction enzyme analysis of cellular oncogenes was performed on DNA of 25 patients. No rearrangements could be demonstrated within or near the genes c-myc, c-myb, c-abl, bcr, c-Ki-ras, and N-ras. No amplifications of these genes nor of N-myc or c-Ha-ras were present. Eight of 21 patients were heterozygote for "rare" Ha-ras allelic restriction fragments that have been associated with an increased risk of developing a malignancy. These patients were clinically indistinguishable from patients lacking these fragments. The breakpoint cluster region (bcr) that is rearranged in all patients with Philadelphia chromosome positive chronic myeloid leukemia, was normal in all cases, including at least one patient with Philadelphia chromosome positive ALL. A 2.8 kb HindIII fragment of a hitherto unknown gene or pseudogene related to v-myb probably derives from the Y chromosome. Nineteen patients were examined for point mutations in the N-ras gene, using a novel synthetic oligonucleotide hybridization assay. In two patients activating point mutations were present, both in positions 1 of the 12th codon. Both patients were somewhat older than the others (16 and 11 years), had L2 morphology, and were shown to have high growth fractions of tumor in their bone marrow.
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PMID:Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood. 301 Nov 51

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93

Mutants and fusion products of the c-abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre-B-lymphoma induction in pristane-treated N-myc transgenic BALB/c mice. A-MuLV induced PCs in 21 of 25 mice with a mean post-pristane latency period of 46 +/- 9 days, compared to 134 +/- 25 days in controls exposed to pristane alone. delta XB, a mutant of type IV c-abl with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 +/- 7 days, indicating that gag sequences are not required for rapid PC induction. The delta XB delta Nar mutant that carried a large C-terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C-terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR-ABL fusion constructs encoding an 185-kDa protein as in acute leukemia, or a 210-kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane-induced PC development in the N-myc transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non-transgenic littermates developed a pre-B lymphoma after A-MuLV infection, and none of 10 normal littermates infected with delta XB virus developed a construct-carrying tumor. This result suggests that PC acceleration is due to co-operative interaction of the N-myc transgene and activated abl. Infection of N-myc transgenic bone marrow or spleen cells with A-MuLV in vitro led to the outgrowth of pre-B lymphomas after transplantation to pristane-treated BALB/c recipients. The lymphoma-inducing activity of A-MuLV depends on its high titer, since diluted A-MuLV or the lower-titered delta XB induced only PCs under the same conditions. The v-abl, delta XB and BCR-ABL-carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N-myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.
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PMID:Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice. 801 9

Oncogenes are genes associated with causation of cancer. They were originally associated with the ability of retroviruses to cause tumors in animals. These viral oncogenes (V-onc) have their cellular counterparts (C-onc) called Proto oncogenes. Function of Proto oncogenes is to maintain cellular growth and development. Activation of these proto-oncogenes can occur due to mutation which leads to uncontrolled cell growth. The Proto oncogenes can be grouped into different categories based on their protein products, i.e. protein kinases, growth factors, growth factor receptors, and DNA binding proteins. There are also genes that normally suppress malignant transformation and these are called anti oncogenes. Loss of their suppressor activity leads to unimpeded growth. Oncogene abnormalities are seen in pediatric leukemias, lymphomas, and various solid tumors. Anti oncogenes are associated with retinoblastoma (Rb gene), Wilms' tumor, rhabdomyosarcoma and neuroblastoma, etc. Identification of these abnormalities have diagnostic, prognostic and therapeutic implications. The utility of oncogenes in classification of human cancer and monitoring cancer therapy is quite clear, but the future of these for therapeutic interventions remains uncertain. Role of c-abl oncogene in chronic myeloid leukemia (CML), bcl-2, in lymphomas, N-myc in neuroblastomas and retinoblastoma (Rb) gene in retinoblastomas is well understood and used in designing proper therapeutic approaches. Since oncogenes also control normal cellular function, their use for therapy may be limited by the amount of damage to normal cells. Their maximum therapeutic benefit may be realized only when used in combination with other modalities.
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PMID:Oncogenes: present status. 824 94