Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present two cases in which translocations involving 21q22 were found at presentation in acute nonlymphocytic leukemia (ANLL). The first of these translocations, t(3;21)(q26-q27;q22), is previously unknown in ANLL, but appears indistinguishable from that reportedly associated with Philadelphia-positive chronic myelogenous leukemia. The second case involves t(15;21)(q21-q22;q22), a translocation previously undescribed in ANLL. Both of these exchanges involve 21q22 plus another chromosome region associated with leukemogenesis. We attempted to interrelate these cytogenetic data with the oncogenic significance of 21q22.
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PMID:Novel translocations in acute nonlymphocytic leukemia. Two cases involving chromosome 21, band q22. 229 84

Certain hematopoietic disorders and immunodeficiency states are known to carry a risk of developing acute nonlymphocytic leukemia. In the past some of them have been classified by a variety of terms ranging from refractory anemia to preleukemia, but are currently grouped into a new concept of the myelodysplastic syndromes (MDS). The purpose of this article is to briefly review the updated knowledge of the MDS with emphasis on the clonal origin, natural history and mechanisms of leukemogenesis.
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PMID:[Preleukemic disorders]. 264 30

Five patients with acute nonlymphocytic leukemia (ANLL) with chromosomal aberrations involving bands 9q21-q22 are described. The abnormalities were an interstitial deletion in two cases of ANLL FAB type M4 and M4 with eosinophilia, a terminal deletion in two cases of M4 and M5 type ANLL, and a translocation in an M2 ANLL. A review of reported cases of ANLL with abnormalities of chromosome 9 revealed a clustering of breaks at the region 9q21-q22, suggesting a possible role for these bands in leukemogenesis.
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PMID:Involvement of bands 9q21-q22 in five cases of acute nonlymphocytic leukemia. 273 Nov 48

Nine cases of overt acute nonlymphocytic leukemia and four cases of preleukemia or a myelodysplastic syndrome, all related to intensive treatment with alkylating agents, were studied cytogenetically and investigated using a rapid and sensitive dot blot screening procedure for point mutations in the Ha-ras, Ki-ras, and N-ras protooncogenes within codons 12, 13, and 61. The technique involves a selective amplification of genomic DNA sequences containing the codon sequence of interest, in combination with oligonucleotide hybridization. Examining fractionated mononuclear cells from bone marrow or peripheral blood, an N-ras mutation at position 13 was observed in one patient with overt leukemia, resulting in a base change from GGT to TGT thus converting glycine to cysteine. The other cases exhibited no ras gene mutations. It is surprising that c-ras mutations are only occasionally observed in overt acute nonlymphocytic leukemia related to treatment with alkylating agents, as such abnormalities have often been observed in acute nonlymphocytic leukemia de novo, and as many alkylating agents are known to produce DNA adducts leading to point mutations and substitution of single amino acids. The fact that deletions of varying parts of the long arms of chromosomes 5 and 7 are observed in most cases of therapy-related acute nonlymphocytic leukemia and preleukemia, as confirmed by our own series of 71 patients, suggests that loss of heterozygosity for specific alleles on the two chromosomes, rather than activation of a protooncogene, could be an important step in leukemogenesis.
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PMID:Point mutation of the ras protooncogenes and chromosome aberrations in acute nonlymphocytic leukemia and preleukemia related to therapy with alkylating agents. 328 Jan 21

Human leukocyte antigen-DP (HLA-DP) typing was performed on patients with chronic myelogenous leukemia (CML, n = 44), acute nonlymphoblastic leukemia (ANLL, n = 34), or acute lymphoblastic leukemia (ALL, n = 41). Frequencies of DPw alleles in CML and ANLL patients were not significantly different from 254 controls, except that in ANNL DPw1 was absent. This was most likely due to the concurrent absence of DR3 with which DPw1 is in linkage. In contrast, in ALL, frequencies of DPw2 and DPw5 were significantly increased (corrected P less than 0.05, relative risk (RR) = 2.19 and corrected P less than 0.01, RR = 6.92, respectively). This was not due to linkage with DR. The frequency of DPw1 also tended to be reduced, but this was not caused by a similar decrease of DR3 in ALL. These results, therefore, demonstrate both positive and negative associations between major histocompatibility complex (MHC) gene products which are in only very weak linkage with the rest of HLA, and acute lymphocytic, but neither acute nor chronic myelogenous, leukemias. The HLA-DP region could thus contain long sought-after genes influencing susceptibility and resistance to leukemogenesis.
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PMID:Human leukocyte antigen-DP in leukemia. 342 71

This report describes a case of a female infant of congenital leukemia with a chromosomal translocation t(11;19) (q23;p13) which presented initially with lymphoid features and at relapse with monocytic ones. The clinical course and the results of sequential cytochemical, cytogenetic and immunological studies are considered to be consistent with the interpretation of leukemogenesis of the myelo-monocytoid progenitor cell which still retains the capability of exhibiting lymphoid features to a limited extent. Although leukemia with t(11;19) has been classified as ANLL, most commonly M5 of FAB classification, the patient with this chromosomal abnormality may have a mixed leukemia in which cells with lymphoid features and those with monocytic ones exist.
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PMID:11;19 translocation in a congenital leukemia with two cell populations of lymphoblasts and monoblasts. 407 55

We evaluated the occurrence of second cancers among 517 patients with non-Hodgkin's lymphoma (NHL) treated at the National Cancer Institute. Nine cases of acute nonlymphocytic leukemia (ANL) were observed compared to 0.08 cases expected (ratio of observed to expected cases, 105; 95% confidence limits, 48; 199). The excess risk of ANL was 4.1 cases per 1000 patients per year; the cumulative risk of ANL at 10 years was 7.9 +/- 3.2% (S.E.). A case-control study within the NHL cohort revealed that patients treated with both radiation and chemotherapy were at greater risk of ANL than were patients who received single-modality therapy (relative risk, 6.0; p less than 0.05), especially if the therapy included total-body or hemibody radiation. A positive correlation between cumulative radiation dose to the bone marrow and risk of ANL was demonstrated, independent of chemotherapy duration. A similar correlation between chemotherapy dose and risk of ANL was suggested but could not be proven with the available data. An apparent association between ANL risk and indolent NHL histological subtypes was due to the significantly larger amounts of potentially leukemogenic therapy to which these patients were repeatedly exposed. Only one case of ANL occurred among NHL patients whose initial therapy produced a durable complete remission. Our data are compatible with a multistep model of leukemogenesis and also underscore the need for curative NHL treatment regimens which minimize the duration and quantity of therapy required for optimum patient management.
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PMID:Evidence of a treatment dose response in acute nonlymphocytic leukemias which occur after therapy of non-Hodgkin's lymphoma. 657 58

A somatic translocation event fusing the novel gene set to the putative oncogene can has been implicated in the development of acute nonlymphocytic leukemia in humans. In this study, full-length cDNAs highly homologous with human set were cloned from a rat neonatal kidney library. The expression pattern of set mRNA was then examined in developing rat kidney. Two groups of set cDNAs (alpha and beta) with different translation initiation sites and open reading frames of 867 and 831 bp, respectively, were found. The predicted protein products are 33,385 and 32,085 Da in size and contain approximately 30% acidic residues, over half of them clustered at the COOH terminal, thus forming a long acidic tail. No signal peptide or membrane-spanning domains were identified, suggesting an intracellular protein product. By ribonuclease protection assay, both alpha and beta variants of set were expressed in kidney. On Northern blots of total kidney RNA, 3.0- and 2.2-kb mRNAs hybridized with the labeled set cDNA probe. Expression of both transcripts was four- to eightfold greater in neonatal compared with adult rat kidney. When neonatal rat kidneys were examined for set mRNA expression by in situ hybridization with 35S-labeled riboprobe, expression was densely localized in the cortical region of morphogenesis over primitive nephron structures, including S-shaped bodies. Thus mRNA for Set, a putative intracellular protein involved in leukemogenesis, is expressed in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spatially restricted expression of set mRNA in developing rat kidney. 750 4

The translocation (6;9) in acute nonlymphocytic leukemia results in the formation of a dek-can fusion gene. In a case of acute undifferentiated leukemia, the oncogene can is fused to a different gene, named set, instead of dek and is assumed to be activated. Transcripts of set encode a putative SET protein with a predicted molecular mass of 32 kDa. We identified SET as a 39-kDa protein by immunoprecipitation with rabbit antiserum against each of three synthetic peptides predicted from the open reading frame of the set gene. We confirmed this identification of SET by protein sequencing. We also observed that SET is expressed ubiquitously in various human cell lines. SET is phosphorylated on serine residue(s) in cultured cells and is localized predominantly in nuclei. Although the function(s) of SET and SET-CAN is not known, we propose that SET plays a key role in the mechanism of leukemogenesis in acute undifferentiated leukemia, perhaps by activating CAN in nuclei and stimulating the transformation potential of SET-CAN. This proposed role would therefore be similar to the roles observed for BCR and DEK of the chimeric oncoproteins BCR-ABL and DEK-CAN in acute myeloid leukemia and acute nonlymphocytic leukemia, respectively.
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PMID:Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia. 829 83

We used the flow cytometric immunoassay to study the correlation between the rumor-suppressor gene product p53- and the DNA ploidy in 30 de novo cases of acute nonlymphocytic leukemia (ANLL). The results showed that 15 cases were positive expression for p53. As compared with p53 negative (p53) cases, the patients with positive p53 (p53+) had higher percentage of bone marrow blasts and lower peripheral leukocyte and platelet counts, which had no influence on the complete remission rate. Before treatment, DNA diploidy was seen in 18 cases including 12 p53- cases, and DNA aneuploidy in 12 cases including 9 p53+. After therapy, aneuploidy could be transformed into diploidy. Patients with P53+ or having aneuploidy in complete remission were at risk for early relapse. We believe that p53 may be involved in the process of leukemogenesis and progression of ANLL.
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PMID:Correlative study on the expression of p53 and DNA ploidy in acute nonlymphocytic leukemia. 873 41


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