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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jumping translocations are an unusual phenomenon and have been rarely reported in leukemia. We report three patients whose leukemic cells had multiple related clones resulting from unbalanced jumping translocations of 1q and 7q to chromosomes 1, 8, 15, 21 and 22. The chromosome findings, together with limited published reports, suggest that jumping translocations are new non-random rearrangements and may represent poor prognostic biological markers. Although their origin is unknown, circumstantial evidence suggests that telomeric ends of receptor chromosomes may play a role in stabilizing jumping translocations in dividing malignant cells.
Leukemia 1995 Apr
PMID:Jumping translocations in leukemia. 772 97

The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previously assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detected in 14 primary acute leukemia or myelodysplasia samples with structural abnormalities of chromosome 20q11, the gene was amplified and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb.
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PMID:Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line. 777 10

A novel human gene, ARCN1, has been identified in chromosome band 11q23.3. It maps approximately 50 kb telomeric to MLL, a gene that is disrupted in a number of leukemia-associated translocation chromosomes. cDNA clones representing ARCN1 hybridize to 4-kb mRNA species present in all tissues tested. Sequencing of cDNAs suggests that at least two forms of mRNA with alternative 5' ends are present within the cell. The mRNA with the longest open reading frame gives rise to a protein of 57 kDa. Although the sequence reported is novel, remarkable similarity is observed with two predicted protein sequences from partial DNA sequences generated by rice (Oryza sativa) and fruit fly (Drosophila melanogaster) genome projects. The degree of sequence conservation is comparable to that observed for highly conserved structural proteins, such as heat shock protein HSP70, and is greater than that of gamma-tubulin and heat shock protein HSP60. A more distant relationship to the group of clathrin-associated proteins suggests a possible role in vesicle structure or trafficking. In view of its ancient pedigree and a potential involvement in cellular architecture, we propose that the ARCN1 protein be named archain.
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PMID:The human archain gene, ARCN1, has highly conserved homologs in rice and Drosophila. 778 67

The gene for hereditary haemochromatosis (HFE) lies telomeric to HLA-A and is believed to be expressed in the intestinal mucosa. Its product has not been characterized, but iron overload and its pathological consequences occur only in homozygotes for this putative gene. The genes encoding the putative human counterparts of the mouse thymus-leukaemia (TL) antigens map to the area where the HFE gene lies. Here, we postulate that a human TL gene may encode a protein acting as or interacting with the transferrin (Tf) receptor in the intestinal mucosa. This hypothesis is based on the following observations: (i) hereditary haemochromatosis (HH) is due to excessive absorption of iron through the intestinal mucosa. HH has a strong association with HLA-A3, but HLA-A3 has no direct role in the pathogenesis and reflects linkage disequilibrium with a telomeric gene. (ii) An HLA-A3 homozygous genotype is associated with the highest relative risks for both early-onset leukaemia and HH. In analogy to the susceptibility locus in mice, this genotype may reflect a TL gene association in leukaemia and raise the possibility of a TL gene involvement in HH. (iii) A TL antigen-like human molecule encoded in the region telomeric to HLA-A, TCA, is expressed in leukaemia and recognized by a Tf receptor-specific monoclonal antibody. The Tf receptor is believed to have a role in the control of intestinal iron absorption. (iv) In mice, particular TL antigens are exclusively expressed in the intestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thymus-leukaemia antigens: the haemochromatosis gene product? 783 88

Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts11 is significantly higher in PCTs induced in pristane-conditioned mice infected by Abelson-murine leukemia virus (52%) compared to those induced by pristane alone (8.1%). Although the significance of Ts11 in mouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically promote the development of PCTs in which both oncogenes, c-myc and v-abl, are abundantly expressed. To test this assumption we induced PCTs by three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1, and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F1, BALB/c-nu/nu, and 5-month-old SCID mice infected with ABL-MYC virus were trisomic for Chr 11. In contrast, < 10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v-myc and v-raf or c-myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenesis. By inducing PCTs in F1 heterozygous mice that are carriers of reciprocal translocations involving Chr 11 we found that the duplicated chromosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this chromosomal segment strongly suggests the presence of a gene or genes whose amplification is of critical importance for v-abl associated murine plasmacytomagenesis.
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PMID:Nonrandom chromosomal change (trisomy 11) in murine plasmacytomas induced by an ABL-MYC retrovirus. 786 5

Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with homology to the zinc fingers and other domains of the Drosophila trithorax gene product and to the "AT-hook" motif of high mobility group proteins. To map potential transcriptional activation or repression domains of the MLL protein, yeast GAL4 DNA-binding domain and MLL hybrid protein-expressing plasmids were cotransfected with chloramphenicol acetyltransferase reporter plasmids in a transient transfection system. We found that MLL contains a strong activation domain and a repression domain. The former, located telomeric (3') to the breakpoint region, activated transcription 18-fold to > 200-fold, depending on the promoter and cell line used for transfection. A repression domain that repressed transcription 4-fold was located centromeric (5') to the breakpoint region of MLL. The MLL AT-hook domain protein was expressed in bacteria and was utilized in a gel mobility shift assay to assess DNA-binding activity. The MLL AT-hook domain could bind cruciform DNA, recognizing structure rather than sequence of the target DNA. In translocations involving MLL, loss of an activation domain with retention of a repression domain and a DNA-binding domain on the der(11) chromosome could alter the expression of downstream target genes, suggesting a potential mechanism of action for MLL in leukemia.
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PMID:11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. 793

People with ataxia telangiectasia (AT) are at a higher than normal risk of T cell leukaemia and often have either non-malignant or malignant T cells with chromosomal abnormalities, typically t(14;14), inversion 14 or more rarely t(X;14). This provides a chance to study the pre-leukaemic phase of the disease. T cells have been studied with either t(14;14)(q11;q32.1) or t(X;14)(q28;q11) from two AT sisters of which the latter developed T cell leukaemia. The telomeric breakpoint of the t(14;14) was cloned and found to occur at 14q32.1 where known tumour-associated breakpoints are located, but the patient remains asymptomatic for leukaemia. Analysis of T cell populations in both patients showed that the cells containing the translocation became oligoclonal with respect to T cell receptor beta rearrangement and complete T cell receptor beta clonality was only established in the patient with t(X;14) by onset of overt disease. Therefore in these chronic diseases, chromosomal translocations can precede T cell receptor rearrangement suggesting a role for these abnormalities as early events of malignant outgrowth.
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PMID:Clonal evolution of malignant and non-malignant T cells carrying t(14;14) and t(X;14) in patients with ataxia telangiectasia. 803 21

Deletion of the retinoblastoma gene (Rb-1) was found in more than 50% (12/23) of patients with multiple myeloma (MM) by fluorescence in situ hybridization (FISH). Myeloma cells were highly purified from bone marrow aspirates by flow cytometry and analyzed using probes specific for the Rb-1 gene and the centromeric region of chromosomes 13 and 21. Routine cytogenetics revealed abnormal chromosome 13 in only 17% (4/23) of these patients. No correlation between Rb-1 deletion and tumor stage, immunoglobulin isotype, anemia, serum beta-2 microglobulin levels, patient age or the extent of prior therapy was found. However, the high incidence of Rb-1 deletion detected by FISH suggests a role of this tumor suppressor gene in the biology of MM. Although allelic loss of the Rb-1 gene is unlikely to be the only genetic change necessary for the development of MM, it may be a relatively early event in MM unrelated to chemotherapeutic intervention. Since the Rb-1 gene suppresses IL-6 production and secretion, Rb-1 deletion may result in deregulation of IL-6 expression and hence expansion of IL-6 dependent myeloma clones.
Leukemia 1994 Aug
PMID:Deletion of the retinoblastoma gene in multiple myeloma. 805 62

In somatic cells, each DNA replication round gives a shortening of the telomere ends as a consequence of incomplete lagging strand synthesis. Telomeres are essential for chromosomal integrity and extensive telomere length reduction is associated with increased instability of the genome. In germ line cells and in established cell lines, telomerase activity maintains the length of the telomeres by de novo synthesis of telomeric repeats, in humans (T2AG3)n. Recently, it was for the first time shown the existence of telomerase activity in human ovarian carcinomas. In the present study we show that telomerase activation can also occur in human hematopoietic tumor cells in vivo. Cell extracts from 19 cases with leukemia, lymphoma and myeloma were tested for telomerase activity using an in vitro assay with (T2AG3)3 or permutations of this sequence as primers. Eight cases demonstrated an RNAse A sensitive ability to add new nucleotides to the human telomere sequence. Nine acute leukemias were tested telomerase negative. Our data demonstrate that telomerase activation in vivo seems to be a common event in B cell neoplasias with a mature immunophenotype like non-Hodgkin's lymphoma and myeloma, in contrast to acute leukemias of B, T or myeloid cell origin. Telomere length evaluation indicated no marked differences between samples with or without telomerase activity which could argue for a telomere length independent mechanism for telomerase activation in at least some cases.
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PMID:Telomerase activity in vivo in human malignant hematopoietic cells. 808 12

We performed conventional cytogenetic (CC) and interphase fluorescence in situ hybridization (FISH) analysis with an alpha satellite chromosome 7 specific DNA centromeric probe (p alpha 7t1) on bone marrow material prepared for CC in 11 controls and 80 cases of myelodysplastic syndromes (MDS). In controls, a mean of 4.3 +/- 1% of the 700 cells examined showed only one FISH signal for chromosome 7, and the finding of > 6.3% (mean +2 standard deviations) of cells with one FISH signal was considered to indicate the presence of a clone with -7. By CC, clonal -7 was found in 11 patients, whereas two patients had -7 in only one mitose (non-clonal -7). In eight of the 11 cases of clonal -7 by CC, interphase FISH confirmed -7. In the remaining three patients, 5.1%, 6.3% and 18.4% respectively of the cells had one signal. Those three patients had, in addition to -7 by CC, a marker chromosome which was shown to be constituted of chromosome 7 pericentromeric material by FISH analysis on metaphase spreads (metaphase FISH). Of the two patients with non-clonal -7 by CC, one had a -7 clone by interphase FISH whereas the other patient had normal FISH results. Five of the 67 patients with no -7 mitose by CC had clonal -7 by interphase FISH, with one chromosome 7 signal in 14.4 to 39% of the cells examined. At least three mitoses with -7 were found in two of them by metaphase FISH. Three of the five patients were reexamined 12 to 17 months later: CC and metaphase FISH found no -7, whereas interphase FISH still showed a -7 clone. Three of the patients with clonal -7 by CC and by FISH were reexamined in complete hematological remission after intensive therapy. CC found no -7 and interphase FISH was normal in all three patients. Our findings suggest that interphase FISH may improve the detection of -7 in MDS. Conventional cytogenetics should still be performed in parallel to FISH, however, because of possible false negative FISH results when a pericentromeric chromosome 7 marker is present in patients with -7. Larger numbers of cases with minor -7 clones, detectable by FISH only, and longer follow-up in those cases will be necessary to determine the significance of this finding, the evolution of this minor clone, and the outcome of the patients.
Leukemia 1994 Jun
PMID:Fluorescence in situ hybridization improves the detection of monosomy 7 in myelodysplastic syndromes. 820 74


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