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)

Beside the frequent aneusomies of chromosomes # 7 and # 8 gains or losses of several other chromosomes are found in bone marrow cells of leukemia patients. Chromosomal heterogeneity of interphase cell populations was studied by fluorescence in situ hybridization (FISH) with centromeric DNA probes for chromosomes #2, #3, #4, #6, #9, #11, #12, #15, #16, #17, #18, #20, as well as X and Y which were found to be aberrant by routine karyotyping of 28 cases of various malignant hematopoietic diseases. Particularly, the data obtained by both routes of analysis were compared quantitatively. As the most prominent result, all aberrations found by classical karyotyping were redetected by interphase cytogenetics, but additional aberrant clones could be observed among the interphase cell populations. The frequencies of the cell clones with hypersomies were in general higher in metaphase than in interphase, and, vice versa, monosomic cells were found more frequently in interphase than in metaphase. Single aberrant karyotypes in all cases were redetected as microclones of interphase cells. Interphase cytogenetics using FISH, therefore, was shown not only to be a reliable measure of the genomic heterogeneity of leukemic cell populations but, in addition, to be a valuable and informative supplement to routine leukemia cytogenetics with regard to the detection of microclones which, later on, could dominate the progression of the malignant disease.
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PMID:Chromosomal heterogeneity of aneuploid leukemic cell populations detected by conventional karyotyping and by fluorescence in situ hybridization (FISH). 826 93

A simplified technique for fluorescent in situ hybridization (FISH) was used to investigate the prevalence of chromosomally abnormal clones in 13 cases of myelodysplastic syndrome (MDS). Biotinylated centromeric probes for chromosomes 7, 8, 12 and X, as well as painting probes for chromosomes 7 and 11, were applied to air-dried bone marrow smears stored from 6 to 23 months. Nine of the cases had been previously karyotyped, and five of these demonstrated normal karyotypes which were confirmed by FISH. The remaining four cases showed different chromosome changes. One case of sideroblastic anemia with chronic lymphocytic leukemia showed minor clones with either monosomy 12 (12% of cells) or tetraploidy (15% of cells) by FISH, whereas metaphase cytogenetics had demonstrated trisomy 12 in 20% of cells, with no evidence of tetraploidy. Another case which had been previously karyotyped was found to have a t(7;11) in 90% of cells while only 10% of cells were shown by FISH to contain this translocation. Monosomy 7 was demonstrated by FISH in a case of refractory anemia (RA), while trisomy 8 was found in a case of RA with excess blasts in transformation (RAEB-T), and in both of these cases the aneuploid clone was present in eosinophils as well as in erythroid and granulocytic precursors but not in lymphocytes or histiocytes, thereby demonstrating the value of FISH for identifying the affected cell lineage.
Leukemia 1994 Jan
PMID:Quantifying chromosome changes and lineage involvement in myelodysplastic syndrome (MDS) using fluorescent in situ hybridization (FISH). 828 3

We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences. All fusion sequences maintained an open reading frame. The areas of the MLL and AF-4 genes that are conserved in all derivative 11 fusion RNAs and therefore likely to contribute to the function of the oncogenic fusion protein are centromeric regions of MLL through exon 6 (retaining the AT hook motif) and telomeric regions of AF-4 beginning at codon 491 (containing nuclear localization and GTP-binding motifs). A single primer pair was able to detect the derivative 11 fusion transcript in seven of seven cases of t(4;11) acute leukemia tested. Given the variability shown in specific fusion sequences, studies correlating differential exon usage with clinical parameters will require different fusion-specific oligonucleotides or PCR primer pairs.
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PMID:Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia. 835 9

We have previously shown that 30% of patients with B-cell chronic lymphocytic leukemia (B-CLL) have hemizygous deletions of the retinoblastoma (RB1) gene at 13q14. RB1 gene deletions may thus participate in malignant transformation of B-CLL, but it is also possible that a neighboring gene on 13q is the relevant one. To answer this question the remaining RB1 allele of eight clones with hemizygous deletions was studied by reverse transcription-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and immunofluorescense techniques. Cells from 10 patients without RB1 gene deletions were also studied by these methods. Lack of RB1 mRNA and RB protein expression was seen in leukemia cells from one of the patients. All other cases were found to be normal with regard to immunofluorescense, RT-PCR, and SSCP analysis, indicating at least one functional RB1 allele and supporting the importance of another gene in the 13q14 deletions. We then performed extended Southern blot analyses of the 13q region, using probes for 10 different loci. In 14 of 31 CLL clones (45%), deletions of a region telomeric to the RB1 gene (D13S25) were observed. In 4 of the cases the deletions were homozygous. Hemizygous deletions of the RB1 gene were observed in 11 of these patients and in none of the patients without D13S25 deletions. These data thus indicate that a gene(s) telomeric to RB1 is involved in the malignant transformation of CLL clones and that deletions of this region are a common event in this disease.
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PMID:Chronic lymphocytic leukemia cells with allelic deletions at 13q14 commonly have one intact RB1 gene: evidence for a role of an adjacent locus. 837 51

Endoglin is a homodimeric membrane glycoprotein primarily associated with human vascular endothelium. It is also found on bone marrow proerythroblasts, activated monocytes and on lymphoblasts in childhood leukemia. Endoglin has recently been described as a component of the transforming growth factor-beta (TGF-beta) receptor system as it can bind TGF-beta 1 with high affinity. We now report on the localization of the human endoglin gene (END) to human chromosome 9, by Southern blot analysis of BglII fragments of DNA from human-hamster somatic cell hybrids. This chromosomal localization was confirmed by fluorescent in situ hybridization coupled with Distamicin A (DA)/4',6-diamidino-2-phenylindole (DAPI) banding on human chromosomes. The regional localization was assigned to 9q34-->qter by GTG-banding (G-banding by trypsin using Giemsa stain), indicating a telomeric position with respect to the Philadelphia breakpoint.
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PMID:Assignment of the human endoglin gene (END) to 9q34-->qter. 840 38

The TCL1 locus on chromosome 14 band q32.1 is frequently involved in the chromosomal translocations and inversions with the T-cell receptor genes observed in several T-cell tumors, including T-prolymphocytic leukemias, acute and chronic leukemias associated with the immunodeficiency syndrome ataxia-telangiectasia, and adult T-cell leukemia. All breakpoints cloned in this area have been mapped to 14q32.1, an area distant approximately 10,000 kb from the immunoglobulin heavy-chain gene locus on chromosome 14q band 32.3. Except for two cases of inversion, no physical linkage of the cloned breakpoints has been reported, nor has a gene been identified in this region. Taking advantage of chromosome-walking techniques and of the P1 phage, we cloned and characterized 450 kb of the germ-line TCL1 locus, starting from the breakpoints of two independent T-cell leukemias. We show that all molecular rearrangements characterized so far map to these clones, indicating not only that this region is the target of chromosomal rearrangements occurring in this area but also that both inversion and translocations occur within a 300-kb region in the T-cell leukemias. In the attempt to identify a candidate oncogene responsible for the malignant transformation, a CpG island centromeric to the inversions and to the translocations has been identified. Two probes near the CpG island have detected sequences conserved among species, as well as two transcripts in the K562 human erythroleukemia cell line. On the basis of these data, a model of activation of the putative TCL1 oncogene is suggested.
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PMID:Chromosome walking on the TCL1 locus involved in T-cell neoplasia. 841 91

Centrocytic lymphoma is a CD5-positive B-cell neoplasm. Rearrangements at the chromosome 11q13 bcl-1 breakpoint loci are present in the majority of these lymphomas, as a result of reciprocal translocation with the 14q32 immunoglobulin heavy chain joining genes. Recently, a gene lying approximately 110 kb telomeric of the bcl-1 major translocation cluster breakpoint locus, designated PRAD1, was proposed as a candidate bcl-1 oncogene. Accumulated evidence now indicates that this gene is the postulated bcl-1 oncogene. It encodes a protein with homology to cyclin family proteins designated cyclin D1 (CCND1). In order to determine whether 11q13 translocation breakpoints were present near the PRAD1 coding region in addition to the previously defined bcl-1 sites, we analyzed 27 centrocytic lymphomas by Southern blot using genomic and cDNA probes flanking the first exon of PRAD1. Five samples showed rearrangement at PRAD1 sites. In four of these, the breakpoints could be mapped from approximately one to 25 kb upstream of the first PRAD1 exon; each showed comigration of rearranged PRAD1 and immunoglobulin heavy-chain joining gene bands consistent with the t(11;14)(q13;q32). The fifth case was rearranged with PRAD1 probes only on BamHI-digested DNA, indicating either a point mutation or a polymorphism at this site. This sample also had rearrangement on multiple enzyme digests with the bcl-1 p94PS probe. None of 80 non-centrocytic B-cell neoplasms showed PRAD1 rearrangement. Thus, rearrangement at both bcl-1 and PRAD1 loci is strongly associated with centrocytic lymphoma, and provides a useful molecular marker for classifying this subtype of lymphoma. Furthermore, translocation-induced aberrant expression of the PRAD1 cyclin may lead to deregulated cell cycle control and play an important role in the pathogenesis of centrocytic lymphoma.
Leukemia 1993 Feb
PMID:Chromosome 11 translocation breakpoints at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma. 842 77

One of the most frequent cytogenetic abnormalities in human leukemia and myelodysplasia is an interstitial deletion within chromosome 5q. A tumor suppressor gene has been hypothesized to lie in 5q31, the smallest commonly deleted region. IRF-1, a gene whose product manifests anti-oncogenic activity, was mapped to 5q31.1. IRF-1 lies between IL-5 and CDC25C and is centromeric to IL-3 and GM-CSF. Among these genes, only IRF-1 was consistently deleted at one or both alleles in 13 cases of leukemia or myelodysplasia with aberrations of 5q31. Inactivating rearrangements of one IRF-1 allele, accompanied by deletion of the second allele, were also identified in one case of acute leukemia. Thus, IRF-1 may be a critically deleted gene in human leukemia and myelodysplasia.
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PMID:Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. 843 56

By circumventing the need for metaphase preparations, fluorescent in situ hybridization (FISH) on interphase nuclei using chromosome-specific probes is a promising tool for the study of numerical chromosome aberrations not only in proliferating, but also in non-dividing cells. We analyzed 15 cases of monosomy-7-associated myeloid disorders with a biotinylated probe to the (peri)centromeric region of chromosome 7. Monosomy 7 was readily confirmed in all cases during active disease. In two patients only a minority of nuclei was monosomic, whereas cytogenetics had shown all metaphases to be missing one chromosome 7. FISH in one of them was able to identify a small marker chromosome as isolated pericentromeric region of chromosome 7. Minimal residual disease however could not be detected in three remission samples analyzed, as percentages of disomic nuclei were within the range of normal controls (96.8% 2.1%). In order to determine lineage involvement of the monosomic clone, a recent technique combining immunophenotyping and FISH (FICTION) was performed in one patient with AML after MPD. Monosomy 7 was found in virtually all myelomonocytic and erythroid cells (as discriminated by lineage-specific antibodies), in a part of CD34-positive precursor cells, but not in lymphocytes. We conclude that monosomy 7 in this patient is restricted to an early committed progenitor cell capable of erythroid and myelomonocytic differentiation.
Leukemia 1993 Mar
PMID:Interphase cytogenetics by fluorescent in situ hybridization (FISH) for characterization of monosomy-7-associated myeloid disorders. 844 44

Early clinical remission of acute lymphoblastic leukemia (ALL) was examined by fluorescence in situ hybridization (FISH) in bone marrow cells from eight patients with high hyperdiploid (> 50 chromosomes) clones at diagnosis. Alphoid centromeric probes to chromosomes X, 10, 17, and 18, trisomic at diagnosis, were used as appropriate. Three hematologically normal marrows were used as controls. At diagnosis, trisomic interphase cells ranged from 69.3-84.4%. One month later, trisomic and tetrasomic interphase cells were significantly increased over control frequencies in 2/7 cases tested (p < 0.05 and p < 0.001) and trisomy alone in one case (p < 0.05). At two months post-diagnosis, trisomy and tetrasomy were in the control range. Pentasomy and hexasomy, not seen in controls, were found in 5/7 samples at one month and in 1/5 samples at two months. One patient examined in chromosomally normal relapse had 34.4% trisomic cells by FISH at confirmed relapse (p < 0.001). An additional hyperdiploid case, examined at central nervous system relapse, had increased numbers of trisomic cells (p < 0.01) in a morphologically and cytogenetically normal marrow. These findings demonstrate the elimination of aberrant ploidy in most hyperdiploid cases two months from diagnosis and indicate that failure to detect the abnormal clone in relapse may result from selective mitotic activity of chromosomally normal cells, rather than relapse in a cytogenetically normal clone.
Leukemia 1993 Apr
PMID:Interphase in situ hybridization reveals minimal residual disease in early remission and return of the diagnostic clone in karyotypically normal relapse of acute lymphoblastic leukemia. 846 32


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