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

Blastic cells of acute lymphoid, acute myeloid and acute myelomonocytic leukaemias were studied by means of indirect immunofluorencence to provide more information on the presence of satellite nucleoli in blood cells. According to results, satellite nucleoli were found in a small but constant number of blastic cells disregarding their type and type of acute leukaemia. Satellite nucleoli exhibited a positive immunoreaction for fibrillarin and protein B23 which are characteristic for main nucleolar components. These findings suggest that satellite nucleoli contain fibrillar centers as well as dense fibrillar and granular components or at least proteins characteristic for these nucleolar components. Similarly as in normal and pathological cells of completely different origin, in blastic cells of acute leukaemias the number of satellite nucleoli per cells ranged between 1 and 2.
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PMID:Studies on satellite nucleoli in human blastic cells of acute leukaemias. 169 84

Dipyridamole (DPM) enhanced sensitivity to doxorubicin (DOX) in a human leukemia cell line that was already relatively sensitive to this agent. Using an immunofluorescence technique, we determined the localization of nucleophosmin (protein B23) in HL-60 cells after incubation with DOX in the absence and presence of DPM. Bright nucleolar fluorescence was observed in control HL-60 cells. The addition of DOX (0.1-0.25 micrograms/ml) in the culture system resulted in time- and dose-dependent induction of nucleophosmin translocation from the nucleolus to nucleoplasm and inhibition of cell growth. DPM (5 microM) alone had no effect on nucleophosmin translocation and inhibition of cell growth. However, the addition of DPM to the cells enhanced DOX-stimulated translocation of nucleophosmin. There was a good correlation between the DPM enhancement of DOX-induced nucleophosmin translocation and the increased inhibition of cell growth. The cell number decreased to a greater extent within a shorter time period under treatment with DOX in the presence of DPM. Short exposure (0.5 hr) of HL-60 cells to DOX induced dose-response nucleophosmin translocation and cell growth inhibition. Such effects of a short exposure to DOX were also enhanced by DPM (5 microM) included in the fresh medium after removal of DOX. This was in agreement with the observation that DPM could increase the cellular DOX by inhibiting the drug efflux from the cells. These results demonstrate that DPM, being able to increase and retain the intracellular levels of DOX, can markedly enhance the cytotoxicity of DOX, and suggest possible clinical application. "Nucleophosmin translocation", as observed by immunofluorescence, could be useful in determining the efficacy of combinations of DOX and DPM in cancer chemotherapy.
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PMID:Dipyridamole enhancement of doxorubicin-induced translocation of nucleophosmin and inhibition of cell growth in HL-60 cells. 191 61

Mouse leukemia cells (p388D1) were grown in medium containing various amounts of mitomycin C for 4 h. Cellular localization of protein B23 was detected using an immunofluorescence technique. Translocation of protein B23 from nucleoli to the nucleoplasm was observed with increasing dose of mitomycin C. To study the correlation of B23 translocation and drug resistance, three human colon carcinoma cell lines, HCT116, HCT116b (a line that is natively or intrinsically resistant to mitomycin C), and HCT116-44 (a line with an acquired resistance to mitomycin C), were employed. These cells were incubated with 1--150 micrograms/ml of mitomycin C. The drug concentration that caused 50% of the cells to have complete translocation (IC50) was determined for each cell line. The IC50 values of HCT116, HCT116b and HCT116-44 were 6, 10 and 50 micrograms/ml, respectively. These IC50 values correlate well with the mitomycin C resistant phenotype of these tumor cells as determined by other in vivo and in vitro assays (Willson, et al. (1985) Cancer Res., 45, 5281-5286). These results identify an inverse relationship between the ease of protein B23 translocation and the degree of mitomycin C resistance in human colon carcinoma cells. This relationship applies to cells that have either acquired mitomycin C resistance or intrinsic resistance to the drug.
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PMID:Assessment of tumor cell sensitivity to mitomycin C by "B23 translocation" assay. 313 7

Anaplastic large cell lymphoma (ALCL) expressing the CD30 antigen is an uncommon subtype of non-Hodgkin's lymphoma characterized by distinct morphological and clinical features. The recurrent chromosomal abnormality found in these tumours is a t(2;5)(p23;q35) which has been detected in a minority of these cases, predominantly with a T cell immunophenotype. We report here a CD30 positive null cell type ALCL case cytogenetically characterized by a new type of t(2;5) translocation with distinct breakpoints at 2q37 and 5q31. FISH with a panel of 5q specific DNA probes applied in this case allowed for a mapping of a 5q31 breakpoint region between the locus for IL-3 (proximally) and CI5-56 probe (distally). These results point to a localization of unknown gene(s) on the long arm of chromosome 5 that, in addition to the NPM gene at 5q35, may be involved in the pathogenesis of some CD30+ ALCL.
Leukemia 1995 Oct
PMID:A new t(2;5) translocation in a null cell type CD30 positive anaplastic large cell lymphoma case. 756 10

Changes in topoisomerase I (topo I) levels and localization were examined during the course of granulocytic maturation in vitro and in vivo. Western blotting revealed that granulocytic maturation in DMSO-treated HL-60 human leukemia cells was accompanied by a 5-fold decrease in topo I polypeptide content. Consistent with this result, 3- to 5-fold higher concentrations of the topo I poison camptothecin were required to stabilize topo I-DNA adducts in DMSO-treated HL-60 cells compared to untreated cells. Northern blotting revealed that these changes occurred without any decrease in topo I message. Immunolocalization studies revealed that these quantitative changes were accompanied by redistribution of topo I away from the nucleoli, where it was prominently accumulated in untreated HL-60 cells, to a more uniform nuclear distribution in DMSO-treated cells. Similar changes occurred during granulocytic maturation in human marrow in vivo. Western blotting revealed that topo I levels in normal progranulocytes were 50% as high as those in HL-60 cells, levels in metamyelocytes were 35% as high as HL-60 cells, and levels in peripheral blood granulocytes were 5% as high as HL-60 cells. Two other polypeptides that are concentrated in nucleoli, poly(ADP-ribose) polymerase and B23/nucleophosmin, also decreased during the course of granulocytic maturation. These changes were accompanied by an alteration in topo I localization similar to that observed in HL-60 cells during the course of granulocytic maturation. Conversely, treatment of human lymphocytes with the mitogenic lectin concanavalin A resulted in a 3-fold increase in topo I polypeptide content concomitant with a prominent increase in the amount of nucleolar antigen. These observations not only provide a context for understanding the recent observation that topo I levels are higher in human leukemia specimens than in normal marrow but also raise the possibility that elevated topo I levels in other cells might reflect alterations in nucleolar structure and function.
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PMID:Changes in topoisomerase I levels and localization during myeloid maturation in vitro and in vivo. 788 18

The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity thought to be related to Hodgkin'S disease (HD), but displaying also its own unique features. Cytogenetic studies of ALCL have demonstrated the presence of a (2;5)(p23;q35) translocation in a substantial number of these cases. Recently, the t(2;5) has been cloned and described to represent fusion of the NPM gene with the ALK gene on chromosome 5. To better define the spectrum of lymphomas containing this abnormality we have analyzed 50 continuous human cell lines established from various types of non-Hodgkin's lymphoma, ALCL and HD. In a first step, the expression of the NPM-ALK fusion gene was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). In a second step, the t(2;5)-carrying cells were tested for the translation of functional chimeric mRNA into a fusion protein by immuno-staining of single cells with a polyclonal antibody. The NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL cell lines. We were unable to find PCR evidence for the t(2;5) in any of the non-ALCL cell lines including other CD30+ cell lines. As all seven bona fide HD cell lines were NPM-ALK-negative, these results do not support the notion that the t(2;5) represents a chromosomal aberration common to both ALCL and HD.
Leukemia 1996 Jan
PMID:The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas: absence of t(2;5) in Hodgkin-analogous cell lines. 855 20

We have previously detected by immunofluorescent assay that the cellular localization of nucleophosmin/B23 (NPM) shifts from the nucleolus to the nucleoplasm (NPM-translocation) after exposure of cells to multiple agents. In order to improve the quantification of the NPM-translocation, we have developed a digital imaging technique. Human Lo leukemia cells, MCF-7 breast carcinoma cells, and fresh human leukemia cells were exposed to anthracyclines or actinomycin D for 4 h. The degree of NPM-translocation was determined and presented as the localization index (LI). Control cells had a LI of about 10, which indicates that the majority of NPM was localized in nucleoli. The LI for drug-treated cells decreased in a dosage- and time-dependent manner. The effect of two classes of anthracycline (daunomycin and aclacinomycin A) and different types of intercalators (daunomycin and actinomycin D) had additive effects on induction of NPM-translocation. The imaging procedure was easily applied to fresh leukemia cells, thus providing useful information regarding drug effects on cancer cells.
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PMID:Quantitation of the nucleophosmin/B23-translocation using imaging analysis. 862 Apr 41

Human T cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) belong to the complex retrovirus whose replication is controlled by trans-acting proteins. HIV-1 encodes several regulatory proteins, including two essential trans-activations for viral replication, Rev and Tat. Both Rev and Tat have a nucleolar targeting signal and are actually located predominantly in the nucleoli. Within the nucleoli, Rev is localized to the combined regions of the dense fibrillar (DFC) and the granular (GC) components. Tat does not colocalize precisely with any nucleolar component tested, but partly overlaps regions of the DFC and the GC. Regions of both Rev and Tat are overlapped by the distribution of the major nucleolar protein B23. Overexpression of Rev causes nucleolar ballooning and general structural deformity with aberrant accumulation of rRNAs, whereas Tat does not have that effect. B23 is markedly accumulated in those nucleoli deformed by Rev. Components of the nucleolar DFC, GC, and fibrillar center domains are not accumulated but dispersed in a few small spots or larger patches within the enlarged nucleoli. Cytophotometric DNA determinations revealed that transient expression of Rev results in accumulation of G2, prophase, and mitotic cells which have failed cytokinesis, suggesting that Rev is capable of preventing or slowing the progression through mitosis. Tat, in contrast, does not affect the cell cycle. We speculate, based on these results, that Rev represses cell growth inhibiting the transport of ribosomal proteins and preribosomal particles across the nuclear envelope and affecting the cell cycle, both of which may be related to the proposed functions of B23.
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PMID:The post-transcriptional regulator Rev of HIV: implications for its interaction with the nucleolar protein B23. 915 Aug 88

All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemic (APL) blasts from patients with t(15;17) APL. However, blasts from patients with the t(11;17) variant do not differentiate in response to ATRA. Our group has identified a variant of APL characterized by t(5;17) and expression of the NPM-RAR fusion gene product. From case reports it has been difficult to establish whether ATRA induces clinical responses in patients with this variant. In order to determine whether t(5;17) blasts differentiate with ATRA, we harvested mononuclear bone marrow cells from a patient with t(5;17) APL at time of relapse and cultured them in medium containing ATRA. Morphologic analysis of cytospins after 7 days of culture revealed that 60% of cells in the ATRA-treated culture had differentiated into mature neutrophilic forms, as opposed to less than 1% in the control culture. Seventy-three percent of cells acquired NBT positivity after exposure to ATRA, compared with 1% in the control culture. These results indicate that t(5;17) blasts retain the ability to terminally differentiate in response to retinoic acid.
Leukemia 1997 Jul
PMID:Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid. 920 84

Interferon regulatory factor-1 (IRF-1) acts as a transcriptional activator in the interferon system and as a tumor suppressor. The loss of functional IRF-1 has been observed in a significant number of patients with myelodysplastic syndrome (MDS) and leukemia, suggesting a potentially critical role of IRF-1 in human oncostasis. Here we report an alternative mechanism by which IRF-1 may be inactivated. We purified an IRF-1 association molecule which was revealed to be identical to a nuclear factor nucleophosmin (NPM)/B23/numatrin. Functional analysis showed that NPM inhibited the DNA-binding and transcriptional activity of IRF-1. Moreover, NPM was overexpressed in several clinical leukemia samples and human-derived leukemia cell lines. Finally, overexpression of NPM in NIH3T3 cells resulted in malignant transformation. These results suggest the possible involvement of NPM in inactivating IRF-1-dependent anti-oncogenic surveillance in human cancer development.
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PMID:Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity. 931 94


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