Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report on 16 cases of either subacute (SMML) or chronic (CMML) myelomonocytic leukemia as well as chronic monocytic leukemia (CMoL). All these cases were oligoblastic and, according to their clinical course, they could be termed as smouldering leukemias. The chronic types affected mainly males. The diagnostic cytomorphological and cytochemical criteria are discussed. Erythro- and thrombocytopoiesis were distinctly less impaired than in acute leukemias (AL). The leucocyte count in the peripheral blood of the SMML cases was within the normal range. Hepato- and splenomegaly were markedly increased as compared to AL. According to our materials leukemic skin infiltrations were less frequent in CMoL, CMML and SMML than in acute monocytic leukemias. In each of the three types of leukemia discussed monocytic leukemic cells could be readily identified by cytochemical tests and usually showed fairly normal maturation. In accordance with these observations lysozyme levels in urine and serum usually were strongly increased. The patients in the CMML and CMoL groups showed a mean survival of more than 13 months (2 out of 7 are still alive), whereas the SMML patients survived an average of 8 months. Deaths were frequently due to advanced age rather than to leukemia. In other cases a terminal accumulation of blasts marked a transition to acute leukemia. During the smouldering phase of the disease no beneficial effect of combined chemotherapy could be noted. Supportive and symptomatic therapy might improve length and quality of survival.
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PMID:[Subacute and chronic monocytic leukemia: diagnostic and clinical problems]. 29 89

All cellular ets proteins contain a region of high amino acid identity to those found in the last two exons of the ets-1 gene (C domain). We have identified and characterized a new member of the human ETS gene family, ERGB. The ERGB gene shows extensive amino acid identity to the human ERG and the mouse Fli-1 genes. The ERGB gene is found to be transcriptionally active in a variety of human cell lines and tissues, in contrast to the more restrictive expression pattern of the ERG gene. The ERGB gene encodes for a 3.2-kilobase mRNA containing an open reading frame of 451 amino acids. The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia. Pulse-field gel analysis suggests that ETS1 and ERGB are more than 200 kilobases apart. Similar to the other members of the ets family (ets 1, ets 2), this new member is also able to trans-activate transcription of a reporter gene linked to the ETS-binding sequences derived from either the GATA-1 promoter or an optimal Ets-binding site.
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PMID:The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors. 144

The human ETS1 proto-oncogene proteins have been isolated from the T-cell leukemia line, CEM, by immunoaffinity chromatography and their identity confirmed by NH2-terminal amino acid sequencing. Incubation of CEM cells with N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) indicates that ETS proteins can be modified in their cellular context and that pretreatment of the cells with N-ethylmaleimide (NEM) protects ETS1 proteins from TLCK modification. These data show that ETS1 proteins can exist in at least two different states, -SH-available and -SH-protected. Renatured human ETS1 has DNA sequence-specific binding to the PEA3 (CAGGAAGT) motif. The ETS1.PEA3 complex can be observed by electrophoretic mobility shift assays (EMSA). Purified ETS1 retards a band which is exactly the same size as a complex that is retarded from nuclear extracts prepared from CEM cells. Reduced ETS1 is required to form the ETS1.PEA3 complex, however; modification of the ETS1 -SH groups by either NEM or by TLCk does not inhibit formation of the complex. The ETS1.PEA3 complex formed with TLCK-modified ETS1 has a slower mobility than the complex formed with unmodified ETS1. Zone sedimentation analysis of purified ETS1 indicates that it is the monomer of ETS1 which binds to the PEA3 oligonucleotide.
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PMID:Human ETS1 oncoprotein. Purification, isoforms, -SH modification, and DNA sequence-specific binding. 151 30

The retroviral integration site Fli-1 is rearranged in 75% of the erythroleukemia cell clones induced by Friend murine leukemia virus (F-MuLV), whereas Spi-1/PU.1, a member of the ets family of DNA-binding proteins, is rearranged in 95% of the erythroleukemias induced by Friend spleen focus-forming virus (SFFV). To determine the transcriptional domain defined by Fli-1, we have isolated a cDNA clone that is highly expressed only in erythroleukemia cell lines with Fli-1 rearrangements. The protein sequence of this cDNA is very similar to Erg2, another member of the ets gene family. The hydrophilic carboxy-terminal end of the Fli-1 cDNA shares significant sequence similarity to the DNA-binding ETS domain found in all members of the ets family. PFGE analysis localized Fli-1 within 240 kb of the ets-1 proto-oncogene on mouse chromosome 9 and human chromosome 11q23, suggesting that ets-1 and Fli-1 arose from a common ancestral gene by gene duplication. The involvement of the murine Fli-1, Spi-1, and avian v-ets genes in erythroleukemia induction suggests that activation of ets gene family members plays an important role in the progression of these multistage malignancies.
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PMID:Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. 204 59

We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX, -21/46, XX, -21, +r(21), who has limited manifestations of Down syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a hematologic disorder particularly common in Down syndrome patients. In situ hybridization studies, gene dosage, and DNA polymorphism analysis showed that the ring chromosome carries a duplicated region which extends from D21S406 on the centromeric side and includes marker D21S3 on the telomeric side. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) probably was formed postzygotically. Included in the duplicated segment are the candidate genes for leukemia AML-1, ETS, and ERG. The potential significance of disomic homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed.
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PMID:Cytogenetic and molecular analysis of a ring (21) in a patient with partial trisomy 21 and megakaryocytic leukemia. 757 23

The PU.1 transcription factor is a member of the ets gene family of regulatory proteins. These molecules play a role in normal development and also have been implicated in malignant processes such as the development of erythroid leukemia. The Ets proteins share a conserved DNA-binding domain (the ETS domain) that recognizes a purine-rich sequence with the core sequence: 5'-C/AGGAA/T-3'. This domain binds to DNA as a monomer, unlike many other DNA-binding proteins. The ETS domain of the PU.1 transcription factor has been crystallized in complex with a 16-base pair oligonucleotide that contains the recognition sequence. The crystals formed in the space group C2 with a = 89.1, b = 101.9, c = 55.6 A, and beta = 111.2 degrees and diffract to at least 2.3 A. There are two complexes in the asymmetric unit. Production of large usable crystals was dependent on the length of both protein and DNA components, the use of oligonucleotides with unpaired A and T bases at the termini, and the presence of polyethylene glycol and zinc acetate in the crystallization solutions. This is the first ETS domain to be crystallized, and the strategy used to crystallize this complex may be useful for other members of the ets family.
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PMID:Co-crystallization of an ETS domain (PU.1) in complex with DNA. Engineering the length of both protein and oligonucleotide. 759 33

Translocations in bands 11q23.3-11q24 are associated with several human cancers, including acute lymphoid and acute myeloid leukemias (AML) and Ewing's sarcoma. We have characterized two independent deletions in this region, one derived from a patient with AML who previously had a T-cell lymphoma, and another from a Wilms' tumor patient. Cytogenetic analysis of the ML-2 cell line established from the malignant cells of the AML patient indicated that one chromosome 11 homolog had an interstitial deletion, del(11) (q23q24), and the remaining homolog was involved in a recurring translocation, t(6;11) (q27;q23). According to karyotype analysis on the Wilms' tumor patient (EH), one chromosome 11 was normal and the other carried an interstitial deletion at 11q23.3-11q25. Somatic cell hybrids segregating the EH deletion (EHR4) and the ML-2 deletion (MLR4) have been isolated. The EH deletion is distal to the MLL probe recently associated with 11q23.3 leukemia breakpoints (Ziemin-van der Poel et al.: Proc Natl Acad Sci USA 88:10735-10739, 1991). The ML-2 deletion could involve the MLL gene at a point distal to other breakpoints within MLL. Both deletions include the Ewing's sarcoma breakpoint at 11q24.1. By Southern blot analysis we identified three anonymous DNA markers (D11S272, D11S273, and D11S219) and the ETS/oncogene, which map within each deleted region. These markers are conserved based on zoo blot analysis, and they are valuable for physical mapping and genetic characterization of a region that may code for gene products associated with growth control and tumor suppression in a variety of cancers.
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PMID:Characterization of two 11q23.3-11q24 deletions and mapping of associated anonymous DNA markers. 768 55

Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia. The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent. The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy.
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PMID:Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. 776 24

The enhancer of Moloney murine leukemia virus (Mo-MuLV) contains an array of transcriptional control elements that direct viral gene expression in diverse cell types. The murine transcription factor Ets-1 was shown to bind to the LVb and LVc elements of the enhancer by DNase I protection and methylation interference assays. Enhancers containing disrupted Ets-1 binding sites were tested in transient expression assays in the murine T-cell line EL4.E1; alterations in the LVb element affected constitutive enhancer activity, while mutation of either the LVb or LVc element disrupted phorbol ester-induced enhancer activity. Members of the ets gene family of proteins display similar DNA-binding properties; therefore, we speculated that ets proteins other than Ets-1 also might bind these elements. Crude nuclear extracts of EL4.E1 cells were assayed to identify the protein(s) that potentially functions at the LVb element. The predominant binding activity was not Ets-1 but rather two independent DNA-protein complexes that comigrated in mobility shift assays. UV cross-linking and denaturing gel electrophoresis sized the two DNA-binding species, which we denoted p55 and p100. Immunoprecipitation combined with UV cross-linking identified p55 as the alpha subunit of GA-binding protein. The DNA-binding properties of p100 and several ets proteins were compared. Similarities suggested that p100 is also an ETS domain protein, possibly Elf-1. This strategy could be used to identify other ETS domain proteins in crude nuclear extracts. These findings suggest multiple ETS domain proteins could regulate gene expression of Mo-MuLV.
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PMID:Identification of ETS domain proteins in murine T lymphocytes that interact with the Moloney murine leukemia virus enhancer. 793 72

The ETS family proteins have a conserved DNA-binding domain and act as transcription factors. Three domains have been recently defined in human ETS-1 proteins and their role could depend upon the nature of alternative transcripts according to whether they possess or lack DNA binding and/or transcriptional activation domain and also point mutation that could affect these important domains. Expression of ETS-1 gene is very complex and is controlled at several levels: the initiation of transcription, alternative splicing, post-translational modification, and protein stability. As a selection apparently exists for ETS-1 gene activation in hematopoietic cells, we investigated a relation between quantitative and qualitative ETS-1 expression and leukemogenesis. Using Northern blot, polymerase chain reaction (PCR), and single strand conformation polymorphism (SSCP) methods, we analyzed quantitative and qualitative ETS-1 expression in a variety of hematological pathologies and cell lines of different origin. Two ETS-1 transcripts of 6.8 and 2.7 kb, resulting from differential polyadenylation site utilization and exhibiting different stability, were observed. We identified, in a great number of patients, the four alternative ETS-1 products, but the relative extent significance of the four transcripts was very different from one patient to another. A non-conservative mutation observed in one case of T-cell acute lymphoblastic leukemia (T-ALL) and in the ETS-1 transactivation domain raised the question of suppressor activity for some ETS-1 products, as it is now known that activators and repressors can be encoded by the same gene and consistently co-expressed in vivo.
Leukemia 1993 Nov
PMID:Quantitative and qualitative variation of ETS-1 transcripts in hematologic malignancies. 823 Dec 46


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