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)

Chronic myelocytic or Ph1-positive acute lymphoblastic leukemias have been analyzed for alterations in a variety of proto-oncogenes and anti-oncogenes implicated in the progression of chronic myeloid leukemia (CML) from its chronic phase to blast crisis. The most frequent genetic change found in disease evolution is an alteration of the p53 gene involving a point mutation, a rearrangement or a deletion. These gene changes are common in myeloid and undifferentiated variants of blast crisis but are usually undetectable in lymphoid leukemic transformants. Other molecular changes also occur in the clonal evolution of CML. The retinoblastoma-susceptibility (Rb) gene is an anti-oncogene. Structural abnormalities of Rb are frequent in all types of human acute leukemia, but are particularly common in Ph1-positive leukemia of lymphoid phenotype including both Ph1-positive ALL and lymphoid blast crisis of CML. Changes in Rb occur early in the transition to blast crisis with loss of Rb protein being the common factor. Mutations in the N-RAS gene also occur, but are rare in typical blast crisis. They are sometimes seen in Ph1-negative myeloid blast crisis. Since changes in the p53 gene are generally associated with progression of disease of a myeloid phenotype and changes in the Rb gene occur more often with a lymphoid phenotype, a particular molecular alteration may influence the character of disease evolution in CML.
 ...
PMID:Molecular mechanisms in the evolution of chronic myelocytic leukemia. 149 27

The retinoblastoma susceptibility gene (RB) is expressed in all lineages of normal hematopoietic cells and plays an important role in controlling cell cycle progression at G1/S. Abnormalities of the RB gene may, therefore, predispose to the development of hematologic malignancies. DNA rearrangement was reported to be present in 1.5-12.1% of cases with primary leukemias and the absence of the RB gene product was also observed in 6.3-23.2%. The abnormalities were frequently observed in blastic crisis of CML, especially of the megakaryoblastic phenotype, AML with monocytic differentiation and Ph1-positive leukemias. These results indicate that abnormalities of RB are relatively common in hematologic malignancies and loss of RB function may contribute to the altered growth of these cells.
 ...
PMID:[Abnormalities of the retinoblastoma susceptibility gene (RB) in hematologic malignancies]. 151 56

Counterflow centrifugal elutriation and immunoblotting techniques were used to study the expression of the retinoblastoma (RB) gene during the cell cycle of BV173 chronic myeloid leukemia (CML) cells. Our data showed that Rb protein started to be phosphorylated at early G1 phase, became hyperphosphorylated when cells progressed to late G1 and S phases during cell cycle, and remained hyperphosphorylated throughout S and G2/M phases. Our data suggest that Rb phosphorylation starts at a more distal point to the G1/S phase boundary in human myeloid leukemia BV173 cells rather than at a point more proximal to the G1/S boundary, as seen in HeLa cells.
 ...
PMID:The phosphorylation of retinoblastoma gene product in human myeloid leukemia cells during the cell cycle. 156 29

The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.
 ...
PMID:Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia. 168 97

To investigate the possible role of the product of the retinoblastoma susceptibility gene, pRB, in leukemogenesis, we examined fresh leukemia cells from 56 cases of primary leukemia (AML, 32; ALL, 12; CML-BC, 9; CLL, 3) for expression of pRB by using an immunoblotting assay with anti-pRB monoclonal antibodies PMG 3-245 or 3-340. Expression of the 70 kDa heat shock protein (Hsp70) was examined simultaneously as an internal control. pRB was found to be absent or expressed at an abnormally low level in 13 of 56 cases. Abnormal expression of pRB was most common in AML (8/32) and CML-BC (4/9), and less common in ALL (1/12). Expression of pRB was not induced in two cases of pRB- AML cultured for 24 h with GM-CSF, indicating that pRB expression could not be induced by increasing the rate of proliferation. The eight cases of AML lacking pRB protein were examined for RB1 mRNA by Northern blot. Two lacked RB1 mRNA and six had a normal-sized mRNA (approximately 4.7 kb), although the amount of RB mRNA was very low in some cases. RB1 gene structure was normal by Southern blot in all eight cases lacking pRB protein which were studied. These results show that lack of pRB expression is relatively common in human myeloid leukemias, and suggests that loss of pRB expression could contribute to the altered growth control of these cells.
 ...
PMID:Heterogeneous expression of the product of the retinoblastoma susceptibility gene in primary human leukemia cells. 188 10

The human retinoblastoma gene (RB) product, which is involved in the control of cell cycle and tumor suppression, is constitutively expressed as a nuclear phosphoprotein in normal human cells. We examined leukemic cells from 22 patients with blast crisis of chronic myelogenous leukemia (CML) for alterations of the RB expression. Western blotting and flow cytometry with anti-RB-protein antibodies showed that all of five cases with megakaryoblastic crisis lacked the expression of the RB-encoded protein, whereas none of 17 cases with the other phenotypes such as myeloblastic or lymphoblastic crisis showed any abnormality. These findings suggest that megakaryoblastic transformation of CML might be lineage-specifically associated with loss of the RB protein.
 ...
PMID:Absence of the human retinoblastoma gene product in the megakaryoblastic crisis of chronic myelogenous leukemia. 193 38

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.
 ...
PMID:[Oncogenes]. 303 83

A GENERAL HYPOTHESIS OF CARCINOGENESIS IS PROPOSED CONSISTING OF THE FOLLOWING FEATURES: (1) It is suggested that all cells possess multiple structural genes (Tr) capable of coding for transforming factors which can release the cell from its normal constraints on growth. (2) In adult cells they are suppressed by diploid pairs of regulatory genes and some of the transforming genes are tissue specific. (3) The Tr loci are temporarily activated at some stage of embryogenesis and possibly during some stage of the cell cycle in adult cells. (4) Spontaneous tumors, or tumors induced by chemicals or radiation, arise as the result of a double mutation of any set of regulatory genes releasing the suppression of the corresponding Tr genes and leading to transformation of the cell. (5) Autosomal dominant hereditary tumors, such as retinoblastoma, are the result of germ-line inheritance of one inactive regulatory gene. Subsequent somatic mutation of the other regulatory gene leads to tumor formation. (6) The Philadelphia chromosome produces inactivation of one regulatory gene by position effect. A somatic mutation of the other leads to chronic myelogenous leukemia. (7) Oncogenic viruses evolved by the extraction of host Tr genes with their conversion to viral transforming genes. As a result, in addition to the above mechanisms, tumors may also be produced by the reintroduction of these genes into susceptible host cells.
 ...
PMID:A general theory of carcinogenesis. 420 43

A possible causal association between chromosome structural change and neoplastic transformation has long been mooted, particularly since chromosomal changes occur frequently in the cells of a variety of malignancies. Only in recent years, however, has the evidence in support of this contention begun to appear convincing, and this has followed from the application of developments in cytogenetic techniques. The advent of methods for revealing specific bands in the human metaphase complement has enabled all the chromosomes and many chromosomal regions to be unambiguously identified, and the recent application of prophase banding methods gives further improvements in resolution. With these techniques, specific constitutional chromosomal deletions or translocations have been discovered in inherited cases of retinoblastoma (del.13q14), Wilms' tumour with aniridia (del.11p13) and renal-cell carcinoma (t(3:8) (p21:q24)), in which each of the chromosomal changes appears to be a dominant factor in inheriting a predisposition to a tissue-specific tumour. A heritability for cancer predisposition is also associated with the inherited chromosomal instability syndromes of Bloom's, Fanconi's anaemia and ataxia telangiectasia, although specific chromosomal changes have not been reported to be associated with the neoplasms in such individuals, except in some cases of lymphoma and leukaemia in ataxia telangiectasia. Specific chromosomal translocations have, however, been recorded in a variety of malignancies, with a particular involvement of chromosomes 22, 14, 8, 15, 17 and 21. However, although many hundreds of patients with the specific 9/22 rearrangement seen in chronic myeloid leukaemia and also those with the 14/8 rearrangement in Burkitt's, and other, lymphomas have been described, no single case in which these rearrangements were present as constitutional changes has been reported. The possible nature of the changes seen at the cytogenetic level in terms of gene content of the chromosomes involved is discussed.
 ...
PMID:Cytogenetics of heritability in cancer. 629 35

We have proposed a hypothetical model to explain the role of chromosomal aberrations in malignant development. In this model we postulate two kinds of chromosomal changes: (1) primary, active changes caused by direct interaction between the oncogenic agent and the hereditary material of the host cell. These changes are mainly somatic mutations, but may also be associated with directed structural changes visible in the microscope; and (2) secondary, passive changes arising randomly by nondisjunction and structural rearrangements. They are followed by selection of cells with changes that amplify the primary change and thus appear as nonrandom chromosome patterns. This hypothesis is discussed in the light of 1827 cases of human malignancy in which we have recently surveyed and systematized chromosomal aberrations. Special support for the idea of somatic mutations as the initiator of malignant development comes from work of Knudson and collaborators in human retinoblastoma. The Ph1 chromosome, predominant during the chronic phase of chronic myeloid leukemia (CML), is proposed as an instance of a primary change, whereas the chromosome changes during the blastic crisis of CML will illustrate the secondary changes. The most common of these secondary changes is actually the doubling of the Ph1 and thus an amplification of the primary change. The increase in number of copies of a specific chromosome reported by Green and collaborators demonstrates that this kind of amplification can result in direct response to the need for a specific gene located in that chromosome.
 ...
PMID:The different origin of primary and secondary chromosome aberrations in cancer. 694 29


1 2 3 4 Next >>