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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multicolor karyotyping procedures, such as multiplex fluorescence in situ hybridization (M-FISH), spectral karyotyping, or color-changing karyotyping, can be used to detect chromosomal rearrangements and marker chromosomes in prenatal diagnosis, peripheral blood cultures, leukemia, and solid tumors, especially in cases where G-banding is not sufficient. A regular M-FISH analysis requires relatively large amounts of labeled DNA (microgram quantities), is not informative in interphase nuclei, hybridization can take up to 2 to 3 days, and unlabeled human chromosome-painting probes are not available commercially. Unique probes (plasmids, PAC), specific for centromeric or subtelomeric chromosomal regions, can replace the painting probes in M-FISH to address specific issues, such as the identification of marker chromosomes and aneuploidies. A set of plasmid probes carrying repetitive sequences specific for the alpha-satellite region of all human chromosomes were combined in a metaphase assay and an interphase assay, allowing identification of aneuploidies in one hybridization step, on a single cytogenetic slide. The fluorophore-dUTP and the labeled antibodies required to label and detect the DNA probes can be prepared in any laboratory. All DNA probes can be easily isolated and labeled using common molecular cytogenetic procedures. Because of the repetitive nature of the probes, hybridization time is short, usually less than 1 hour, and the analysis can be performed with nonspecialized image-processing software.
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PMID:Small marker chromosome identification in metaphase and interphase using centromeric multiplex fish (CM-FISH). 1130 66

The t(4;11) translocation is the cytogenetic hallmark of a subset of acute lymphoblastic leukemias characterized by pro-B immunophenotype and a dismal prognosis. This translocation fuses the MLL gene on chromosome band 11q23 and the AF4 gene on 4q21, resulting in the expression of fusion transcripts from both translocated chromosomes. The MLL-AF4 chimeric transcript is thought to mediate the leukemic transformation. The MLL genomic disruption detected by Southern blot and the RT-PCR for the MLL-AF4 chimeric transcript expression are molecular evidence of this chromosomal translocation. However, similar molecular rearrangements have also been identified in cases without the cytogenetic t(4;11). We report a 30-year-old patient with high risk ALL, a normal karyotype, and molecular evidence of MLL-AF4 fusion. Using a double color FISH assay with MLL specific PAC probes, a cryptic t(4;11) due to insertion of 5' MLL sequences in chromosome 4q21 was demonstrated. Consequently the MLL-AF4 was encoded by der(4). This insertion mechanism precludes the genomic recombination of AF4-MLL and supports the crucial role played by MLL-AF4 in leukemogenesis. The findings of our case, along with others, show the importance of complementing the karyotype with molecular and FISH techniques.
Leukemia 2001 Apr
PMID:Cryptic t(4;11) encoding MLL-AF4 due to insertion of 5' MLL sequences in chromosome 4. 1136 62

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine involved in early conceptus development in pig. We isolated a PAC clone containing the porcine LIF gene and determined the complete DNA sequence of the gene, which spans about 6.3 kb and consists of five exons including three alternative first exons (1D, 1M, 1T) spliced onto common second and third exons. The LIF-D transcript encodes a protein of 202 amino acids sharing 87, 84, and 78% identity with respectively human, ovine, and murine leukemia inhibitory factors. The LIF-M and LIF-T transcripts both encode a truncated protein of 158 amino acids. Two SNP markers within untranslated regions of the LIF cDNA were identified. One SNP is located in the 5'-UTR of the alternative exon 1T while the other SNP is located in the 3'-UTR of exon 3. Based on fluorescence in situ hybridization and radiation hybrid mapping, the porcine LIF gene was assigned to chromosome 14q2.1-->q2.2.
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PMID:Molecular characterization and chromosome assignment of the porcine gene for leukemia inhibitory factor LIF. 1147 86

Structural alterations in 3q27 affecting the BCL6 locus are among the most frequent changes in B-NHL. The aim of the present study was to establish an interphase-FISH assay for the detection of all diverse BCL6 translocations in B-NHL. Two different approaches were tested, one using a PAC-clone spanning the major breakpoint region (MBR) of BCL6 (span-assay), and another using two BAC clones flanking the MBR (flank-assay). Interphase FISH with the span-assay detected the various BCL6 translocations in seven B-NHL cell lines. The dual-color flank-assay was evaluated in two laboratories independently: in normal controls, the cutoff level for false-positive signals was 2.6%, whereas the cutoff level for false-negatives in the seven cell lines was 7.5%. To test the feasibility of the FISH strategies, 30 samples from patients with B-NHL with cytogenetic abnormalities of 3q27 were evaluated with both assays. In 21 cases, the span-assay indicated a BCL6 rearrangement. In 18 of the 21 cases, the dual-color flank-assay confirmed the translocation including 12 different partner chromosomal loci. The three false-positive cases detected with the span-assay showed trisomy of chromosome 3 by cytogenetic analyses, and they were correctly classified as non-rearranged with the flank-assay. In summary, our FISH strategy using two differently labeled flanking BCL6 BAC probes provides a robust, sensitive, and reproducible method for the detection of common and uncommon abnormalities of BCL6 gene in interphase nuclei. The routine application of this assay to patients with B-NHL will allow the assessment of the diagnostic and prognostic significance of BCL6 rearrangements.
Leukemia 2001 Sep
PMID:Detection of translocations affecting the BCL6 locus in B cell non-Hodgkin's lymphoma by interphase fluorescence in situ hybridization. 1151 11

Chromosome band 6q21 is reported to be one of the most frequent target regions in T-cell lymphoma for both translocations and deletions. To explore whether the breakpoint clustering in T-cell malignancy indicates the presence of a common breakpoint region in 6q, we employed fluorescence in situ hybridization analysis using various YAC, BAC, and PAC clones aligned at 6q21-22. We identified two T-cell lymphoma/leukemia cell lines with different differentiation stages that had breakpoints within the same novel gene, TCBA1 (T-cell lymphoma breakpoint associated target 1). In a T-cell lymphoblastic lymphoma cell line, HT-1, the TCBA1 fused to SUSP1 (SUMO-1-specific protease), creating a SUSP1-TCBA1 chimeric gene. However, in an adult T-cell leukemia cell line, ATN-1, no chimeric gene was detected, although aberrant TCBA1 transcripts were produced. We conclude that TCBA1 is a possible target gene for T-cell lineage-specific chromosome aberrations at 6q21.
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PMID:Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines. 1197 51

We investigated the potential role of defective DNA-mismatch repair (MMR) as a mediator of leukemogenic susceptibility in patients with therapy-related myelodysplasia (t-MDS) and leukemia (t-leuk). Thirty-seven individuals with t-MDS/t-leuk were analyzed for microsatellite instability (MSI), the hallmark of defective DNA-MMR. Using standardized international criteria, 5/37 (14%) patients displayed high MSI, whereas 3 other patients had low MSI (8%). To determine the stage at which MSI had developed, we analyzed the primary tumors of 12 patients. Three of 4 patients with high MSI t-MDS/t-leuk also had microsatellite unstable primary tumors. Conversely, MSI was not detected in any primary malignancy of patients with low MSI or microsatellite stable t-MDS/t-leuk (P = 0.0182). In the high MSI group, we further investigated genes targeted by defective DNA-MMR (BAX, TGFBRII, IGFIIR, Caspase-5, APC, PTEN, E2F4, MBD4, MSH6, and MSH3) in both primary tumor and t-MDS/t-leuk. However, no mutation was found in any gene. The significant association of MSI in t-MDS/t-leuk and corresponding primary tumors suggests that defective DNA-MMR confers leukemogenic susceptibility to this cohort of patients.
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PMID:Defective DNA-mismatch repair: a potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia. 1197 58

Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4(+) T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2(-/-) mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.
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PMID:CD19 signaling pathways play a major role for murine AIDS induction and progression. 1242 39

The recurrent translocation t(1;3)(p36;q21) is associated with myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and a poor prognosis. Recently, the two genes involved in this translocation have been identified: the MEL1 gene at 1p36.3, and the RPN1 gene at 3q21. The breakpoint in RPN1 is centromeric to the breakpoint cluster region of the inv(3) abnormality. Because the MEL1 transcript is detected only in leukemic cells with t(1;3)(p36;q21), ectopic expression of MEL1 driven by RPN1 at 3q21 is thought to contribute to the pathogenesis of t(1;3)(p36;q21) leukemia. However, the precise breakpoint in the patients has not yet been identified. With fluorescence in situ hybridization analysis by use of BAC/PAC probes, we identified the breakpoint at 1p36.3 in three MDS/AML patients with t(1;3)(p36;q21): within the first intron of the MEL1 gene (one patient) or within a 29-kb region located in the 5' region of MEL1 (two other patients). We detected several sizes of MEL1 transcript in two patients including the first patient, although we have not yet clarified whether MEL1 transcripts were different among the patients and whether a truncated MEL1 transcript was expressed in the first patient. This patient showed an unusual clinical profile, repeating progression to overt leukemia and conversion to MDS three times during the 29-month survival period, which might be related to a different molecular mechanism in this patient.
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PMID:Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1. 1255 31

Differentiation therapy for myeloid leukemia offers great potential as a supplement to the current treatment modalities. In the present report, we investigated if the pyranocoumarins, (+/-)-4'- O-acetyl-3'- O-angeloyl- cis-khellactone (or angular pyranocoumarin, APC) isolated from the medicinal plant Peucedanum praeruptorum Dunn, could induce human acute myeloid leukemic HL-60 cells to differentiate and elucidated the molecular mechanism(s) involved. The ability of HL-60 cells to reduce nitroblue tetrazolium (NBT) was significantly increased after APC treatment for 72 h. In these differentiating HL-60 cells, cell surface differentiation markers CD11b (for myeloid cells) and CD14 (for monocytic cells) were detected in 90.3 % and 70.1 % of the cells, respectively. The differentiation inducing effect of APC was time- and dose-dependent. Treatment with 20 microg/mL APC for 72 h inhibited cell growth by 90 % and cell cycle analysis revealed an increase in the proportion of G1 phase cells. In these growth-inhibited cells the expression of the cyclin-dependent kinase inhibitor p27 kip1, but not p21 WAF1, was up-regulated as shown by Western blotting. Differentiation inducing signal pathways were investigated and it was shown that phospho-MEK and phospho-ERK were elevated shortly after the addition of APC. Pre-incubation of the cells with MEK1 inhibitor PD98059 blocked this APC-induced differentiation. Our results suggest that APC are potent inducers of HL-60 cell differentiation along both the myelocytic and monocytic lineages and are potential agents for differentiation-treatment of leukemia.
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PMID:Pyranocoumarins isolated from Peucedanum praeruptorum as differentiation inducers in human leukemic HL-60 cells. 1267 25

Methylation profile was analyzed in eleven cases of therapy-related leukemia (t-leukemia) for p14, p15, p16, Rb, hMLH1, hMSH2, MGMT, APC, RAR beta, DAPK, RIZ1, FHIT, and SOCS-1 genes by using methylation specific polymerase chain reaction (MSP) analysis. Six (55%) of eleven cases showed methylation of at least one gene. The average time to the development of t-leukemia after the treatment of the primary tumor was significantly shorter in patients with methylation than those without methylation (49.3 months vs. 133.2 months, P=0.044). These results suggest that hypermethylation might be involved in the development of t-leukemia.
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PMID:Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia. 1288 5


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