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M C Sweeney

Publications and source records attributed to M C Sweeney.

4 recordsLinked to original sources
PubMed2000

High FUS/TLS expression in acute myeloid leukaemia samples.

Retinoic acid has the ability to induce differentiation in some myeloid leukaemia cell lines and has been used to induce remission in acute promyelocytic leukaemia patients. We have analysed changes in gene expression, by differential display, in HL60 cells exposed to all-trans retinoic acid (ATRA) for only 1 h. Only about 0.4% of the genes examined by this technique showed changes in expression level, and all four of the gene fragments identified were downregulated during the short 1 h exposure. Two of the fragments were novel, a third was MYC and the fourth was the FUS proto-oncogene. Northern analysis showed that FUS was downregulated within 1 h only during induced neutrophil differentiation but not at all during induced monocyte differentiation. Unlike the sensitive cell lines, ATRA-resistant cell lines did not show a downregulation of FUS over a 24 h period of exposure to ATRA. Using a semiquantitative PCR analysis, no difference in FUS levels was observed between ATRA-sensitive and -resistant cell lines. A similar analysis was carried out on primary acute myeloid leukaemia (AML), peripheral stem cell harvests (PBSC) and cord blood samples. The PBSC and cord blood samples had FUS levels that were similar or generally less than the cell lines. However, much higher levels were seen in 63% of the AML samples examined. The data presented are consistent with previous reports for a role for FUS in the promotion and maintenance of cellular proliferation.

Acute Disease↗
PubMed1999

Inhibition of mitochondrial function in HL60 cells is associated with an increased apoptosis and expression of CD14.

The myelomonocytic cell line HL60 can be induced by a variety of chemical agents to differentiation to either neutrophils or monocytes. Examination of gene expression, by differential display, in cells induced to monocytes with 1alpha,25-dihydroxyvitamin D(3) or neutrophils with all-trans retinoic acid (ATRA) identified a number of clones with altered patterns of expression over the period of differentiation. One of these clones was the mitochondrial gene NADH dehydrogenase subunit 4 (ND4) which showed a differential pattern of expression between the neutrophil and monocyte lineages. The potential of mitochondrial inhibitors to induce differentiation was investigated by treating the HL60 cells with either the NADH dehydrogenase inhibitor, Rotenone, the complex III inhibitor, Antimycin A, or the highly specific mitochondrial ATP-synthase inhibitor, Oligomycin. Although functional assays of differentiation did not produce any positive results, all the inhibitors resulted in a dramatic increase in CD14 expression at day 1, with CD38 markers not observed until day 3. The increased expression of CD14 was accompanied by a decrease in viability and all CD14 positive cells were also positive for Annexin V, a marker of apoptosis. These results suggest that inhibition of the components of the mitochondrial pathways may lead to the marking of some cells, via CD14, for cell death, whilst allowing commitment to differentiation to occur in the surviving population.

ADP-ribosyl Cyclase↗
PubMed1993

Detection of male cells in mixtures containing varying proportions of male and female cells by fluorescence in situ hybridization and G-banding.

The efficiency and sensitivity of fluorescence in situ hybridization (FISH) and G-banding for the detection of male cells in mixtures of male and female cells derived from peripheral blood (PB) and bone marrow (BM) are compared. Zero false positive and negative rates were obtained with G-banding in all studies. False positive rates obtained with FISH were low (0-2.5%) in both PB and BM. False negative rates varied from 0-13.3%. Variations due to differences in fluorescent counterstain or scorers were not significant and in some cases the percentage of Y-positive cells as determined by FISH agreed more closely with the estimated frequency of male cells than that obtained by G-banding. The minimum limits of detection for FISH were 5% male cells on counting 500 PB or BM interphases; 10% male cells on counting 100 PB metaphases; and 20% male cells on counting 50 BM metaphases. This is in agreement with the theoretical limits of detection [95% confidence limit (CL)]. However, minimum levels of detection for female cells were below the 95% CL. It was not possible to reliably distinguish 95% female cells from 100% on counting 500 PB or BM interphases; 90% from 100% on counting 100 PB metaphases; or 80% from 100% on counting 50 BM metaphases.

Bone Marrow↗