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

Cytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole-arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed--monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole-arm or near-centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor prognosis.
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PMID:Fluorescence in situ hybridization analysis of whole-arm 7;12 translocations in hematologic malignancies. 852 85

Lumbosacral chordomas are rare skeletal sarcomas of the spine that originate from the remnant notochord. The understanding of this human cancer is limited to observations of its clinical behavior and its embryonic link. Thus, we performed chromosome and molecular analyses from five surgically harvested chordomas in an effort to document genetic and biochemical abnormalities which might aid in understanding the tumor biology of this understudied neoplasm. Cytogenetic analysis of the five chordomas revealed normal results in four patients and random abnormalities in only one tumor cell in the 100 cells studied from the fifth patient. A repeat telomeric probe (TTAGGG)50 was hybridized to genomic DNA isolated from chordoma cells (and HeLa cells) and digested with HinfI. The tumor DNA was paired with leukocyte DNA from age-matched controls and revealed telomere elongation in four of the four chordoma patients studied with molecular genetic techniques. Conversely, telomere length reduction has been reported during in vitro senescence of human fibroblasts, giant cell tumor of bone, colon cancer, intracranial tumors, childhood leukemia, Wilms tumor, and in HeLa cells. Telomerase activity (telomerase is required to maintain telomere integrity) was also determined by visualizing the extension of radioactive telomeric repeats on DNA sequencing gels. The telomeric fragments were assembled during incubation of the cytoplasmic extract containing telomerase. Telomerase activity was observed in HeLa (positive control and commercially available cell line), giant cell tumor of bone (positive control tumor cells from living patients), and in chordoma cells from one of the two chordoma patients (but to a lesser degree compared with HeLa). As expected, the chordoma patients' fibroblasts exhibited no telomerase activity.
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PMID:Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas. 853 38

Interphase-FISH (fluorescence in situ hybridization) studies have been devoted to the determination of clonality of aberrant karyotypes in human leukemia. Various levels of its extent have been examined, including the meaning of a single aberrant karyotype as representing a microclone, the use of FISH to confirm clonality in bi- or multiclonal leukemia, the estimation of the residual (aberrant) clone after contrasexual bone marrow transplantation, and the redetectability in interphase of the abl/bcr rearrangement. The quantitative findings of all these lines of interphase FISH analyses were based on the comparison with data from a large-scale "control" study on normal cells using the same DNA probes which have been chosen for the determination of clonality, i.e. centromeric DNA probes for chromosomes #1, #3, from #6 to #12, from #15 to #18, #20, X and Y, and a specific probe for the abl/bcr rearrangement. In addition, the validity of interphase-FISH analysis on classical bone marrow smears was examined. As a common outcome it was concluded that interphase-FISH technique is a valuable tool for defining clonality of karyotypic changes and, as a consequence, yields additional prognostic information in many human leukemias. It is recommended to perform interphase FISH in routine cytogenetics of leukemia, whenever reasonable.
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PMID:Determination by interphase-FISH of the clonality of aberrant karyotypes in human hematopoietic neoplasias. 858 Jul 99

Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with regions of homology to several other proteins including the zinc fingers and other domains of the Drosophila trithorax gene product, and the "AT-hook" DNA-binding motif of high mobility group proteins. We have previously demonstrated that MLL contains transcriptional activation and repression domains using a GAL4 fusion protein system (21). The repression domain, which is capable of repressing transcription 3-5-fold, is located centromeric to the breakpoint region of MLL. The activation domain, located telomeric to the breakpoint region, activated transcription from a variety of promoters including ones containing only basal promoter elements. The level of activation was very high, ranging from 10-fold to more than 300-fold, depending on the promoter and cell line used for transient transfection. In translocations involving MLL, the protein produced from the der(11) chromosome which contains the critical junction for leukemogenesis includes the AT-hook domain and the repression domain. We assessed the DNA binding capability of the MLL AT-hook domain using bacterially expressed and purified AT-hook protein. In a gel mobility shift assay, the MLL AT-hook domain could bind cruciform DNA, recognizing structure rather than sequence of the target DNA. This binding could be specifically competed with Hoechst 33258 dye and with distamycin. In a nitrocellulose protein-DNA binding assay, the MLL AT-hook domain could bind to AT-rich SARs, but not to non-SAR DNA fragments. The role that the AT-hook binding to DNA may play in vivo is unclear, but it is likely that DNA binding could affect downstream gene regulation. The AT-hook domain retained on the der(11) would potentially recognize a different DNA target than the one normally recognized by the intact MLL protein. Furthermore, loss of an activation domain while retaining a repression domain on the der(11) chromosome could alter the expression of various downstream target genes, suggesting potential mechanisms of action for MLL in leukemia.
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PMID:The mixed lineage leukemia (MLL) protein involved in 11q23 translocations contains a domain that binds cruciform DNA and scaffold attachment region (SAR) DNA. 858 57

Southern blot analysis with a cDNA probe of MLL indicated that the breakpoint is in a BamHI 8.3 kb fragment which carries the exon 5-11 of MLL gene in DNA from an adult acute myelomonocytic leukaemia with a t(11;22) (q23;q11) translocation. The structural analysis of the rearranged MLL locus demonstrated that the breakpoint is localized between exon 8 and 9 of MLL locus. The normal counterpart fused to the MLL locus was proved to be derived from chromosome 22q11(AF-22) by somatic cell hybrids analysis and FISH. By FISH, AF-22 was localized to the region more centromeric to the BCR gene.
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PMID:Molecular cloning of the breakpoint of t(11;22) (q23;q11) chromosome translocation in an adult acute myelomonocytic leukaemia. 861 37

A major unresolved question for 11q23 translocations involving MLL is the chromosomal mechanism(s) leading to these translocations. We have mapped breakpoints within the 8.3-kb BamHI breakpoint cluster region in 31 patients with acute lymphoblastic leukemia and acute myeloid leukemia (AML) de novo and in 8 t-AML patients. In 23 of 31 leukemia de novo patients, MLL breakpoints mapped to the centromeric half (4.57 kb) of the breakpoint cluster region, whereas those in eight de novo patients mapped to the telomeric half (3.87 kb). In contrast, only two t-AML breakpoints mapped in the centromeric half, whereas six mapped in the telomeric half. The difference in distribution of the leukemia de novo breakpoints is statistically significant (P = .02). A similar difference in distribution of breakpoints between de novo patients and t-AML patients has been reported by others. We identified a low- or weak-affinity scaffold attachment region (SAR) mapping just centromeric to the breakpoint cluster region, and a high-affinity SAR mapping within the telomeric half of the breakpoint cluster region. Using high stringency criteria to define in vitro vertebrate topoisomerase II (topo II) consensus sites, one topo II site mapped adjacent to the telomeric SAR, whereas six mapped within the SAR. Therefore, 74% of leukemia de novo and 25% of t-AML breakpoints map to the centromeric half of the breakpoint cluster region map between the two SARs; in contrast, 26% of the leukemia de novo and 75% of the t-AML patient breakpoints map to the telomeric half of the breakpoint cluster region that contains both the telomeric SAR and the topo II sites. Thus, the chromatin structure of the MLL breakpoint cluster region may be important in determining the distribution of the breakpoints. The data suggest that the mechanism(s) leading to translocations may differ in leukemia de novo and in t-AML.
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PMID:Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites. 863 39

A zinc-finger gene encoding a transcription factor that regulates hematopoiesis, MZF-1, is located at the extreme end of the q arm of human chromosome 19. Several lines of evidence indicate that MZF-1 lies less than 20 kb from the subtelomeric repeat region of 19q. Telomeres are known to degenerate as cells age; disruption of MZF-1 due to telomeric degeneration may play a role in the increased incidence of leukemia in the elderly.
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PMID:The location of MZF-1 at the telomere of human chromosome 19q makes it vulnerable to degeneration in aging cells. 863 24

To discriminate with molecular-cytogenetic resolution between 3q26.2 breakpoint, associated to various myeloproliferative disorders, and 3q27 breakpoint, recurrent in several types of non-Hodgkin lymphoma, we tested the feasibility of using a yeast artificial chromosome, YAC clone H10, mapped on 3q26.3. Fluorescent in situ hybridization of the biotinylated polymerase chain reaction product of the YAC H10 was performed in three myeloproliferative diseases and one follicular non-Hodgkin lymphoma carrying different rearrangements of chromosome 3 involving region q26-q27. Our study shows that YAC H10 signal was telomeric to all three myeloid breakpoints, while it was centromeric in the lymphoid one thus showing that this probe can discriminate between these two subsets of chromosome 3 rearrangements. These results point out the opportunity of using additional YACs in the characterization of polymorphic chromosome alterations acquired in neoplastic cells.
Leukemia 1996 Feb
PMID:YAC clone H10 discriminates between 3q26.2 and 3q27 chromosome rearrangements in hematological disorders. 863 30

The EVI1 gene, located at chromosome band 3q26, is overexpressed in some myeloid leukemia patients with breakpoints either 5' of the gene in the t(3;3)(q21;q26) or 3' of the gene in the inv(3)(q21q26). EVI1 is also expressed as part of a fusion transcript with the transcription factor AML1 in the t(3;21)(q26;q22), associated with myeloid leukemia. In cells with t(3;21), additional fusion transcripts are AML1-MDS1 and AML1-MDS1-EVI1. MDS1 is located at 3q26 170-400 kb upstream (telomeric) of EVI1 in the chromosomal region in which some of the breakpoints 5' of EVI1 have been mapped. MDS1 has been identified as a single gene as well as a previously unreported exon(s) of EVI1 We have analyzed the relationship between MDS1 and EVI1 to determine whether they are two separate genes. In this report, we present evidence indicating that MDS1 exists in normal tissues both as a unique transcript and as a normal fusion transcript with EVI1, with an additional 188 codons at the 5' end of the previously reported EVI1 open reading frame. This additional region has about 40% homology at the amino acid level with the PR domain of the retinoblastoma-interacting zinc-finger protein RIZ. These results are important in view of the fact that EVI1 and MDS1 are involved in leukemia associated with chromosomal translocation breakpoints in the region between these genes.
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PMID:Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family. 864 84

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.
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PMID:Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. 864 22


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