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)

Leukemic cells from all human chronic granulocytic leukemia (CGL) and some acute myelomonocytic leukemia (AMML) donors are lysed by rabbit antisera to a purified glycoprotein of Friend murine leukemia virus (FLV gp71) in a microcytotoxicity assay. These antisera are not cytotoxic to cells from patients with acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or to peripheral blood lymphocytes from normal donors. A goat antiserum to gradient purified FLV in addition to reacting with cells from CGL and AMML donors also reacted with cells from AML patients and some ALL donors. However, this antiserum failed to react with cells from CLL patients. Peripheral blood and bone marrow leukocytes prepared from leukemic patients in clinical remission failed to react with antisera to FLV and FLV gp71. Absorption experiments demonstrated that the antigen on CGL cells which is reacting with the antiserum to FLV gp71 is also present on normal human platelets and neutrophils. Similar absorption studies showed that the antigen on AML cells detected by the FLV antiserum is not present on normal leukocytes and platelets and appears to be related to the major internal p30 antigens of mammalian RNA tumor viruses. Another antigenic relationship between oncornaviruses and membrane antigens of human leukemia cells was shown by the ability of FLV antigens to absorb the cytotoxic reactivity of nonhuman primate antisera detecting human leukemia-associated antigens. FLV and FLV gp71 antigens were able to absorb all cytotoxic activity of monkey and chimpanzee antisera to human myeloid leukemia antigens when these antisera were tested with CGL cells. These two approaches to an analysis of cross-reactivity indicate that the antigenic determinant(s) detected by the cytotoxic reactions of the FLV gp71 antiserum with human CGL cells is different from the determinant on FLV gp71 which is responsible for the inhibition of the reactivity of simian antisera with CGL cells. Since the goat and rabbit antisera to FLV and FLV gp71 are able to distinguish AML from CGL cells by direct cytotoxicity testing and absorption, they may be valuable reagents for the serological diagnosis of myeloid leukemia. In addition, since peripheral blood cells from AML and CGL patients in clinical remission were seronegative, the antisera may be valuable as management aids. The data in this report indicates that whatever the mechanism of leukemogenesis is in man, cells from CGL and AML patients possess certain membrane antigens which cross-react with FLV structural components such as p30 and gp71.
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PMID:Relationships between membrane antigens of human leukemic cells and oncogenic RNA virus structural components. 5 69

Chronic myelogenous leukemia (CML) is a relatively rare disease, with a number of features that make it especially suitable for observations on leukemogenesis in man. These include known etiologic agents, often a prolonged preclinical and active stage, cells with identifiable morphological and histochemical characteristics and the presence of the unique Ph' chromosome. The transition of CML to blast crisis is a catastrophic event; however, recent clinical and biochemical studies have raised important questions as to the nature and origin of blast cells in this disease. During the past 10 years, we have followed 113 cases olf CML throughout their course and results of observations on the clinical, hematological and other apsects of the disease are presented in this communication.
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PMID:Chronic myelogenous leukemia. 27 37

A case of epithelial thymoma occurring synchronously with Philadelphia chromosome-positive chronic myelogenous leukemia and urinary bladder carcinoma in a 76-year-old man is described. Thymomas have been associated with numberous hematologic, collagen-vascular and autoimmune disease states, as well as with an increased incidence of nonthymic malignancy. Human thymoma-associated leukemia is, however, extremely unusual, despite the well-documented role of the thymus in leukemogenesis in experimental animals. No previous literature reports of thymoma associated with chronic myelogeneous leukemia were found. A review of long-term followup data of surviving thymoma patients is necessary to determine if an increased propensity to develop leukemia is present in present in patients with thymoma.
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PMID:Thymoma and chronic myelogenous leukemia: a case report. 106 82

Chromosome analyses were performed by a direct method on bone marrow cells of 147 patients with acute leukemia and preleukemia; in 53 chromosomally abnormal cell lines were found. Chromosome abnormalities due to structural alterations were observed in 48% of the aneuploid patients. Using the ASG banding technique, the exact identification of the abnormal chromosomes was successfully made in 22 aneuploid patients. Even though variability between patients existed in the chromosome changes; the nonrandom occurrence of some chromosome abnormalities was revealed, involving most frequently chromosomes No. 8 and No. 21. Abnormalities of chromosome No. 22 were not encountered, contrasting sharply with the frequent involvement of this chromosome in chronic myelogenous leukemia. The significance of the preferential involvement of No. 8 and No. 21 chromosomes is discussed in relation to leukemogenesis.
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PMID:Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia. 126 Jan 29

Chronic myelogenous leukemia and one type of acute lymphoblastic leukemia are characterized by a 9;22 chronosome translocation in which 5' sequences of the bcr gene become fused to the c-abl proto-oncogene. The resulting chimeric genes encode bcr/abl fusion proteins which have deregulated tyrosine kinase activity and appear to play an important role in induction of these leukemias. A series of bcr/abl genes were constructed in which nested deletions of the bcr gene were fused to the c-abl gene. The fusion proteins encoded by these genes were assayed for autophosphorylation in vivo and for differences in subcellular localization. Our results demonstrate that bcr sequences activate two functions of c-abl; the tyrosine kinase activity and a previously undescribed microfilament-binding function. Two regions of bcr which activate these functions to different degrees have been mapped: amino acids 1 to 63 were strongly activating and amino acids 64 to 509 were weakly activating. The tyrosine kinase and microfilament-binding functions were not interdependent, as a kinase defective bcr/abl mutant still associated with actin filaments and a bcr/abl mutant lacking actin association still had deregulated kinase activity. Modification of actin filament functions by the bcr/abl tyrosine kinase may be an important event in leukemogenesis.
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PMID:Activation of tyrosinase kinase and microfilament-binding functions of c-abl by bcr sequences in bcr/abl fusion proteins. 170 8

The Philadelphia (Ph) translocation is responsible for the generation of the chimeric BCR/ABL oncogene. The Ph chromosome constitutes the earliest detectable chromosome abnormality in chronic myelogenous leukemia and is also found in acute lymphoblastic leukemia. Mice transgenic for a P190 BCR/ABL-producing DNA construct develop lymphoblastic leukemia/lymphoma and provide an opportunity to study early stages of the disease as well as progression. In this study, we have karyotyped the bone marrow of 10 19-day-old BCR/ABL P190 transgenic mice from a line that reproducibly develops leukemia/lymphoma. Leukemic cells from 17 terminally ill transgenic founders and progeny were also karyotyped as well as bone marrow transplant recipients of leukemic donor marrow. Karyotypically visible aberrations were absent from the early stages of BCR/ABL P190-generated leukemia and normal metaphases could be found even in the terminal stages of the disease. A high frequency of aneuploidy was found in advanced leukemia, with a marked preference for the gain of mouse chromosomes 12, 14, or 17. These results point to a primary role for BCR/ABL in leukemogenesis and suggest a destabilizing effect of the BCR/ABL gene on the regulation of cell division.
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PMID:Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice. 173 87

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.
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PMID:Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. 187 48

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.
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PMID:Heterogeneous expression of the product of the retinoblastoma susceptibility gene in primary human leukemia cells. 188 10

N-ras oncogenes activated by point mutation have been frequently detected in various types of human leukemias. Analysis of a large number of leukemias revealed that activated N-ras oncogenes were observed preferentially in AML, AMoL, T-ALL and Null-ALL but rarely in CML and B-cell leukemia. These results suggest that N-ras oncogene plays an important role in human leukemogenesis. Activated N-ras oncogenes were also detected in myelodysplastic syndrome (MDS) that is considered to be a preleukemic disease. MDS patients bearing an activated N-ras oncogene frequently showed leukemic progression of the disease, suggesting that an activated N-ras oncogene can be a critical factor for prognosis of MDS patients. Thus, detection of an activated N-ras oncogene is useful for diagnosis, prognostic evaluation and therapeutic decision. Recently, we demonstrated that detection of the minimal residual disease by analysis of N-ras oncogene can lead to improvement of the remission rate in leukemias. Moreover, we made it possible to screen N-ras oncogene by a sensitive non-radioactive method. Our research procedure seems to be a good model for clinical application of the molecular biological technique.
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PMID:[Activation of ras oncogene in myelodysplastic syndrome and acute myelogenous leukemia]. 205 67

Although determination of chromosomal abnormalities may be of limited usefulness for the diagnosis of leukemia, the recent advances in the molecular mechanism associated with chromosome aberration has been rapid. Chromosome translocation in Burkitt lymphoma and chronic myeloid leukemia was the most striking evidence for the oncogene activation. Other specific chromosome abnormalities for FAB-classified leukemias are also known. Translocated type of chromosome abnormalities between immunoglobulin or T-cell receptor genes and oncogenes may also affect the T and B-cell leukemogenesis. However, the role of trisomies found in human and experimental leukemias and the gene dosages had been thought to be most important until 1982, has not been unclear. Many types of phenotypically heterogeneous leukemias have been reported. t(4 ; 11) acute leukemia is one such leukemia which shows early B-cell and myelomonocytic nature. Heterogeneous leukemias have been called biphenotypic, hybrid and acute mixed leukemias. The terminology must be used the unified. Recent trials to use paraffin-fixed tissues and bone marrow smear for molecular analysis has been successfully reported. Basic analysis on the DNA degradation mechanism revealed the enzymatic activity might play an important role before the complete fixation.
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PMID:[Chromosome aberrations and genes in human and experimental leukemias]. 219 1


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