Biomedical subjects

K S Chang

Publications and source records attributed to K S Chang.

At least 73 records · Page 4Linked to original sources

PubMed1995

PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu.

The chromosomal translocation t(15;17)(q22;q12) is a consistent feature of acute promyelocytic leukemia (APL) that results in the disruption of genes for the zinc finger transcription factor PML and the retinoic acid receptor alpha (RAR alpha). We have previously shown that PML is a growth suppressor and is able to suppress transformation of NIH/3T3 by activated neu oncogene. In the study presented here, the full-length PML cDNA was transfected into B104-1-1 cells (NIH/3T3 cells transformed by the activated neu oncogene) by retrovirally mediated gene transfer. We found that expression of PML could reverse phenotypes of B104-1-1 including morphology, contact-limiting properties, and growth rate in both transient-expression and stable transfectants. We also demonstrated that PML is able to suppress clonogenicity of B104-1-1 in soft agar assay and tumorigenicity in nude mice. These results strongly support our previous finding that PML is a transformation or growth suppressor. Our results further demonstrate that expression of PML in B104-1-1 cells has little effect on cell cycle distribution. Western blot analysis demonstrated that suppression of neu expression in B104-1-1 by PML was insignificant in the transient transfection experiment but significant in the PML stable transfectants. This study suggests that PML may suppress neu expression and block signaling events associated with activated neu. This study supports our hypothesis that disruption of the normal function of PML, a growth or transformation suppressor, is a critical event in APL leukomogenesis.

3T3 Cells↗

PubMed1995

Acute hemodynamic improvement by thermal vasodilation in congestive heart failure.

BACKGROUND: A warm-water bath (WWB) or sauna bath (SB) has generally been considered inappropriate for patients with severe congestive heart failure (CHF). However, a comprehensive investigation of the hemodynamic effects of thermal vasodilation in CHF has not been previously undertaken. METHODS AND RESULTS: To investigate the acute hemodynamic effects of thermal vasodilation in CHF, we studied 34 patients with chronic CHF (mean age, 58 +/- 14 years). Clinical stages were New York Heart Association functional class II in 2, III in 19, and IV in 13 patients. Mean ejection fraction was 25 +/- 9%. After a Swan-Ganz catheter was inserted via the right jugular vein, the patient had a WWB for 10 minutes at 41 degrees C or an SB for 15 minutes at 60 degrees C. Blood pressure, ECG, echo-Doppler, expiration gas, and intracardiac pressures were recorded before, during, and 30 minutes after each bath. Oxygen consumption increased mildly, pulmonary arterial blood temperature increased by 1.2 degrees C, and heart rate increased by 20 to 25 beats per minute on average at the end of WWB or SB. Systolic blood pressure showed no significant change. Diastolic blood pressure decreased significantly during SB (P < .01). Cardiac and stroke indexes increased and systemic vascular resistances decreased significantly during and after WWB and SB (P < .01). Mean pulmonary artery, mean pulmonary capillary wedge, and mean right atrial pressures increased significantly during WWB (P < .05) but decreased significantly during SB (P < .05). These pressures decreased significantly from the control level after each bath (P < .01). Mitral regurgitation associated with CHF decreased during and 30 minutes after each bath. Cardiac dimensions decreased and left ventricular ejection fraction increased significantly after WWB and SB. In an additional study, plasma norepinephrine increased significantly during SB in healthy control subjects and in patients with CHF and returned to control levels by 30 minutes after SB. CONCLUSIONS: Hemodynamics improve after WWB or SB in patients with chronic CHF. This is attributable to the reduction in cardiac preload and afterload. Thus, thermal vasodilation can be applied with little risk if appropriately performed and may provide a new nonpharmacological therapy for CHF.

Adolescent↗

PubMed1995

The intensity of a fetal taste aversion is modulated by the anesthesia used during conditioning.

Rat fetuses (E18) can learn a taste aversion in utero if experience with a sweet flavor (saccharin = Sac) is followed by a malaise-producing injection of lithium chloride (LiCl). Here we report that this phenomenon can be significantly modulated by the type of anesthesia administered to the pregnant dam before the conditioning procedure. Dams were anesthetized with one of the following drugs or drug combinations: (1) sodium pentobarbital; (2) ketamine hydrochloride and xylazine; or (3) sodium pentobarbital and ketamine hydrochloride. While under the influence of these anesthetics, rat fetuses received pairings of Sac + LiCl or one of the following sets of oral and systemic (i.p.) control injections: Sac + Saline, H2O + LiCl; H2O + Saline. At age 15 days neonatal rats were given a taste preference test by allowing them to select nipples painted with either saccharin or vehicle (H2O). After weaning, rats were given an additional taste preference test where they were allowed to drink from bottles filled with either 0.30% saccharin or water. Neonates that received Sac + LiCl injections avoided saccharin-painted nipples while neonates that received control injections in utero preferred saccharin-painted nipples. Rats that acquired the taste aversion under the influence of ketamine showed a significantly stronger conditioned taste aversion on the nipple preference test than did those from dams injected with sodium pentobarbital. The conditioned taste aversion was not detectable later during the bottle preference test. Since ketamine blocks N-methyl-D-aspartate (NMDA) glutamate receptors, and these receptors have been implicated in neural plasticity during development, our data suggest that NMDA antagonism can potentiate fetal learning. Ketamine has been used as an obstetrical and pediatric anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

PubMed1995

Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse.

The translocation between chromosomes 15 and 17, t(15;17)(q22-24;q11-21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

Base Sequence↗

PubMed1995

Interaction of native and asialo rat sublingual glycoproteins with lectins.

The binding properties of the rat sublingual glycoprotein (RSL) and its asialo product with lectins were characterized by quantitative precipitin(QPA) and precipitin inhibition(QPIA) assays. Among twenty lectins tested for QPA, native RSL reacted well only with Artocarpus integrifolia (jacalin), but weakly or not at all with the other lectins. However, its asialo product (asialo-RSL) reacted strongly with many Gal and GalNAc specific lectins-it bound best to three of the GalNAc alpha 1-->Ser/Thr (Tn) and/or Gal beta 1-->4GlcNAc (II) active lectins [jacalin, Wistaria floribunda and Ricinus communis agglutinins] and completely precipitated each of these three lectins. Asialo-RSL also reacted well with Abrus precatorius, Glycine max, Bauhinia purpurea alba, and Maclura pomifera agglutinins, and abrin-a, but not with Arachis hypogeae and Dolichos biflorus agglutinins. The interaction between asialo-RSL and lectins were inhibited by either Gal beta 1-->4GlcNAc, p-NO2-phenyl alpha-GalNAc or both. The mapping of the precipitation and inhibition profiles leads to the conclusion that the asialo rat sublingual glycoprotein provides important ligands for II (Gal beta 1-->4GlcNAc beta 1-->) and Tn (GalNAc alpha 1-->Ser/Thr) active lectins.

Animals↗

PubMed1995

Microwave-induced lethal heat stress: effects of phentolamine, prazosin and metoprolol.

Previous studies have shown that adrenergic antagonists can alter physiological responses to microwave-induced heating. In the present experiments, 33 ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/sq cm (whole-body average specific absorption rate of approximately 14 W/kg) until death occurred. The effects of intraarterial injections of the nonselective alpha-adrenoceptor antagonist phentolamine (10 mg/kg body weight), the alpha 1-adrenoceptor antagonist prazosin (5 mg/kg), and the beta 1-adrenoceptor antagonist metoprolol (2 mg/kg) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. A group of saline-injected animals was included for comparison. There were no significant differences in lethal temperatures, survival times, or rates of temperature change among the different groups. In all groups, heart rate increased continuously during exposure; mean arterial blood pressure increased until colonic temperature reached 41-41.5 degrees C, and then decreased. These heart rate and blood pressure changes were similar to those that occur during environmental heat stress. Despite differences in absolute values of heart rate and mean arterial blood pressure among groups, there were no significant differences in changes from baseline levels among groups. From these results, taken together with previous findings in our laboratory, it may be hypothesized that selective alpha 1 blockade (without concurrent alpha 2 blockade) and beta 2 blockade (with or without concurrent beta 1 blockade) are effective in altering physiological responses to microwave exposure.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1995

Biological characteristics of human hepatocellular carcinoma cell lines with or without prior nude mouse passages.

A cell line, J5, derived directly from the human hepatocellular carcinoma (HCC) by in vitro culture, and three other lines, J2-23, J3-27 and J3-28, which were established in culture only after passages in nude mice were examined. Since nude mice as well as various strains of normal mice often produce infectious murine retroviruses, the HCC cells passaged as a heterotransplant in nude mice may be infected with these viruses. The supernatant of the J2-23, J3-27 and J3-28 cell co-cultured with a wild mouse cell line, SC-1, which supports the murine ecotropic retroviruses, showed the presence of a murine N-tropic virus. No murine xenotropic retrovirus was detected in these cells using S+L- mink cell assay method. A clone (J3-28 Clone 1) was derived from the above mentioned J3-28 cells, since the latter contained a mixture of human and murine cells. The J3-28 Clone 1 was found to be entirely of human karyotype. This clone as well as the J5 and the PLC/PRF/5 cel lines which have never been passaged in nude mice, showed none of these murine retroviruses. By Southern-blot hybridization, no change was detectable for c-abl, c-ras, c-mos, and c-myc protooncogenes in the chromosomal DNA of J2-23, J3-27, J3-28 Clone 1, and J5 cell lines. The karyotypes of all the HCC cell lines were aneuploid, and those of the J2-23 and J3-27 cell lines were of mouse, while the J3-28 Clone 1 and J5 cell lines were of human. The chromosomes of the J2-23 and J3-27 cells showed, except for the presence of a few marker chromosomes in the former, no apparent changes in the length were observed. In contrast, those of the J3-28 Clone 1 and J5 cells exhibited various changes, including 6-8 marker chromosomes, and an increase or decrease in the length of p and/or q arms of various chromosomes.

Animals↗

PubMed1994

Detection of a novel lactate dehydrogenase isozyme and an apparent differentiation-associated shift in isozyme profile in hepatoma cell lines.

A hitherto unreported lactate dehydrogenase (LD) isoenzyme, which migrates electrophoretically to the relative position between LD2 and LD3 has been identified in the electropheratogram in 7 of 7 (100%) cultured hepatoma cell lines with various degrees of differentiation and is thus given the name LD2-3. LD2-3 seems to be specific for hepatoma cells because this atypical isoenzyme can not be detected in other tumor cell lines. In addition, the hepatoma cell lines also show a distinct pattern of LD isoenzyme and the isoenzyme pattern varies with the degree of differentiation. Hence, the expression pattern of LD isoenzyme phenotypes may provide a good marker for the investigation of human hepatoma cell differentiation.

Carcinoma, Hepatocellular↗

PubMed1994

Regulation of the expression of annexin VIII in acute promyelocytic leukemia.

Annexin VIII is a calcium-dependent phospholipid-binding protein previously identified as a blood anticoagulant based on in vitro studies. However, the physiologic function of annexin VIII remains unknown. In acute promyelocytic leukemia (APL) the annexin VIII gene is highly expressed, but its expression is undetectable in the blasts of other acute leukemias. In the present investigation, we showed using the APL-derived NB4 cell line that expression of the annexin VIII gene is regulated at the transcription level during induced differentiation by all-trans retinoic acid (ATRA). The half-life of the annexin VIII mRNA is about 5 to 6 hours, as determined by using actinomycin D as a transcription inhibitor. Analysis of the expression of annexin VIII protein in NB4 cells and in APL samples showed a consistent expression of a predominant 36-kD protein and a weak 72-kD protein. After ATRA-induced differentiation of NB4 cells, the annexin VIII protein level reduced gradually, but a detectable level persisted even after 4 days of induction. Because annexin VIII mRNA becomes undetectable after 48 hours of ATRA induction, this result indicates that annexin VIII is a relatively stable protein. A multiple tissue Northern blot analysis was performed, and we found that annexin VIII is normally expressed in the placenta and the lung. Cellular localization of the annexin VIII protein was determined by immunofluorescence staining and subcellular fractionation. These results indicated that annexin VIII is predominantly localized to the plasma membrane. The annexin VIII is neither an extracellular protein nor associated with the cell surface suggesting that it does not play a role in blood coagulation in vivo. The plasma membrane localization and its property as a phospholipase inhibitor suggests that annexin VIII may have a role in the signal transduction pathway in the APL cells.

Annexins↗

PubMed1994

Molecular subtypes of env sequences around V3 region of human immunodeficiency virus type 1 in Taiwan.

Samples of peripheral blood mononuclear cells (PBMC) were collected during 1990-91 from seropositive healthy, male HIV-1 carriers visiting Taipei Venereal Disease Control Center, and a male AIDS patient admitted to a general hospital. The V3 and its flanking nucleotide (nt) sequences in their DNA were amplified by polymerase chain reaction (PCR) and compared with those of known HIV-1 prototypes. The nt sequences obtained from 21 individuals (e.g., TW92) clustered as Group A, which were highly homologous (95.6-99.5%) to that of HXB2 virus while those from 6 individuals (TW90, TW91, TW97, TW99, TW102 and TW104) were classified as Group B showing low similarities (73.2-84.2%) to those of HXB2 and moderate similarities (80.7-90.0%) to those of SC and Bangkok (BK) viruses. By comparison of their deduced amino acid sequences with those of consensus sequences for subtypes A-F as defined by Myers et al. (1993), both Groups A and B viruses (except TW102) together with those of HXB2, SC and BK viruses could be identified as members or variants of subtype B, and the TW102 virus as a member of subtype E viruses. Individuals with the Group A viruses included 4 homosexual and 17 heterosexual Taiwanese males, 2 of the latter having a history of i.v. drug abuse. Among individuals with Group B viruses, those with TW97, TW99, TW104 and TW91, who was an AIDS patient, were heterosexual Taiwanese males, whereas both TW90 and TW102 viruses were from individuals who were overseas heterosexual Chinese from Thailand, the former with a history of i.v. drug abuse and the latter without.

Acquired Immunodeficiency Syndrome↗

PubMed1994

PML, a growth suppressor disrupted in acute promyelocytic leukemia.

The nonrandom chromosomal translocation t(15;17)(q22;q21) in acute promyelocytic leukemia (APL) juxtaposes the genes for retinoic acid receptor alpha (RAR alpha) and the putative zinc finger transcription factor PML. The breakpoint site encodes fusion protein PML-RAR alpha, which is able to form a heterodimer with PML. It was hypothesized that PML-RAR alpha is a dominant negative inhibitor of PML. Inactivation of PML function in APL may play a critical role in APL pathogenesis. Our results demonstrated that PML, but not PML-RAR alpha, is a growth suppressor. This is supported by the following findings: (i) PML suppressed anchorage-independent growth of APL-derived NB4 cells on soft agar and tumorigenicity in nude mice, (ii) PML suppressed the oncogenic transformation of rat embryo fibroblasts by cooperative oncogenes, and (iii) PML suppressed transformation of NIH 3T3 cells by the activated neu oncogene. Cotransfection of PML with PML-RAR alpha resulted in a significant reduction in PML's transformation suppressor function in vivo, indicating that the fusion protein can be a dominant negative inhibitor of PML function in APL cells. This observation was further supported by the finding that cotransfection of PML and PML-RAR alpha resulted in altered normal cellular localization of PML. Our results also demonstrated that PML, but not PML-RAR alpha, is a promoter-specific transcription suppressor. Therefore, we hypothesized that disruption of the PML gene, a growth or transformation suppressor, by the t(15;17) translocation in APL is one of the critical events in leukemogenesis.

Animals↗

PubMed1994

Clinically relevant concentrations of bupivacaine inhibit rat aortic baroreceptors.

Bupivacaine is clinically associated with cardiovascular toxicity. To examine the possible role of drug actions at arterial baroreceptors, we studied discharge properties of baroreceptors in an in vitro aortic nerve-aortic arch preparation from rats. We measured single fiber discharge, pressure, and aortic diameter simultaneously during perfusion of the aortic arch with bupivacaine. Perfusion mean arterial pressure was held at 80 mm Hg. Only regularly discharging, presumably myelinated, baroreceptors were studied. To assess pressure threshold, threshold frequency, and maximum discharge rate, nerve activity was evoked by slow ramps of increasing pressure (< 2 mm Hg/s) beginning at 20 mm Hg and ranging up to 150-170 mm Hg. Following replicate control measurements, test ramps were repeated in the presence of sodium nitroprusside (1 microM) and phentolamine (1 microM) to eliminate potential smooth muscle and alpha 1-adrenoceptor effects, respectively. Bupivacaine was then added to the perfusate in increasing concentrations from 0.1 to 50 microM for 15 min to construct a full concentration-response curve at each level. Individual baroreceptors showed substantial depression of maximum discharge frequency and/or increases in pressure threshold at 1-5 microM bupivacaine. In overall population averages (n = 7), 5-10 microM bupivacaine clearly reduced maximum discharge and shifted the pressure threshold to higher values (P < 0.01). The net result was a general depression of discharge. Concentrations as low as 10 microM bupivacaine completely blocked discharge in some baroreceptors. Inasmuch as the pressure-diameter relations were not changed, discharge relations plotted against diameter showed equivalent changes. Bupivacaine-free solution reversed the block in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Midazolam produces vasodilation by mixed endothelium-dependent and -independent mechanisms.

Aortic rings were obtained from rat thoracic aorta and studied in vitro with and without functionally intact endothelium to determine whether "the mechanism" requires endothelium [or endothelium-derived relaxing factor (EDRF)]. In aortic rings precontracted with either phenylephrine (PE, 3 x 10(-8)-3 x 10(-7) mol/L) or KCl (40 mmol/L), midazolam produced concentration-dependent relaxation, with and without endothelium. Rings without endothelium demonstrated significantly less relaxation than those with endothelium regardless of whether they were precontracted with PE or KCl. With intact endothelium, midazolam produced greater relaxation in PE-contracted aortic rings than in KCl-contracted aortic rings; the midazolam concentration producing 50% relaxation from the contracted state (RC50) was 8.8 +/- 3.6 x 10(-7) mol/L for PE-contracted rings and 3.3 +/- 1.1 x 10(-6) mol/L for KCl-contracted rings (P < 0.05). In aortic rings with intact endothelium pretreated with NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L), an inhibitor of nitric oxide (NO) synthesis, midazolam produced relaxation of similar magnitude to that seen in the denuded aortic rings except at the highest concentration (1 x 10(-5) mol/L). Pretreatment with the cyclooxygenase inhibitor, indomethacin (2.5 x 10(-5) mol/L), did not change the midazolam-induced relaxation in rings with intact endothelium as compared to untreated control aortic rings. In contrast to the intact endothelium state, when endothelium was removed, midazolam produced greater relaxation in the KCl-contracted aortic rings than in PE-contracted rings (RC50, 1.2 +/- 0.3 x 10(-5) mol/L vs 2.3 +/- 0.4 x 10(-5) mol/L, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Expression of the annexin VIII gene in acute promyelocytic leukemia.

Annexin VIII is preferentially expressed in APL, but its level of expression in other subtypes of AML is much lower. Annexin VIII was originally found to be a vascular anticoagulant, but evidence obtained from our recent studies suggests that it does not play a role in hemorrhage diathesis in APL. The specific expression of annexin VIII in APL may relate to its possible role in hematopoietic cell differentiation. The expression of annexin VIII is developmentally regulated in APL-derived NB4 cells. It can be downregulated as a response to induction by ATRA, an agent which is also capable of inducing maturation of NB4 cells. Our current understanding is that annexin VIII is most likely involved in signal transduction and may have a role as a modulator of PKC. A change in cellular PKC activity is expected to have a significant impact on cell differentiation and proliferation. The biological function of annexin VIII is currently unknown, but its expression in APL and its possible role in differentiation and proliferation of the leukemia cells would provide an excellent model system to study and elucidate this intriguing question.

Amino Acid Sequence↗

PubMed1994

Detection of AML1/ETO fusion transcript as a tool for diagnosing t(8;21) positive acute myelogenous leukemia.

The nonrandom chromosomal translocation t(8;21)(q22;q22) can be found frequently in acute myelogenous leukemia with maturation (AML-M2). The breakpoint of this translocation has been cloned and characterized, and fusion transcript AML1/ETO has been identified. Reverse transcription polymerase chain reaction (RT-PCR) can be used to amplify the breakpoint site of AML1/ETO in t(8;21)-positive AML-M2 patients. The chimeric transcript can be detected in all 16 (100%) t(8;21)-positive AML-M2 patients. In all samples, the size of the amplified DNA fragments and pattern of restriction digest were identical, indicating that the t(8;21) translocation breakpoint occurs within a single intron of the AML1 and ETO genes. Interestingly, this fusion transcript was also detected in one of 13 AML-M2 patients without the t(8;21) translocation, indicating that a masked translocation involving chromosomes 8 and 21, exists in AML. Minimal residual disease was detected by semi-nested RT-PCR in all four patients tested, who had been in complete remission for 12, 15, 34, and 52 months, respectively. These results indicate that RT-PCR amplification of the AML1/ETO fusion transcript is a powerful tool for diagnosing and monitoring minimal residual disease in AML-M2 patients.

Adolescent↗

PubMed1994

Postmortem chorionic villus sampling for cytogenetic evaluation of early fetal loss: a simple reliable method.

BACKGROUND: Early fetal losses associated with chromosome abnormalities produce most spontaneous abortions. It is not feasible to conduct cytogenetic studies with tissue culture postmortem because of tissue maceration and autolysis. METHODS: A total of 30 specimens from early fetal losses were karyotyped for chromosomal study. Success rate of the culture method is evaluated and compared. RESULTS: The abnormal karyotype rate was 33.3%. It was found that chorionic villus tissues had a higher culture rate than tests of fetal skin, amnion or amniocyte by early amniocentesis. CONCLUSIONS: Postmortem chorionic villus sampling at the time of diagnosis of early fetal death appears to offer the best, most simple and reliable method for obtaining a cytogenetic result, and also a good method for training residents in the chorionic villus sampling technique.

Adult↗

PubMed1993

Regulation of HIV-1 LTR trans-activating activities in two different human hepatocellular carcinoma cell lines.

The regulation of trans-activating activities of two human hepatocellular carcinoma cell (HCC) lines, HEP-G2 and SK-HEP-1, was investigated. These cells were transfected with the wild-type and a nested series of its 5'-deletion mutants of the long terminal (LTR) repeat derived from HIV-1, which were ligated with the chloramphenicol acetyl transferase gene. These two HCC cell lines exhibited different biological characteristics, reflecting their status of differentiation. Both cell lines showed moderate degrees of constitutive (basal) trans-activating activities. While HEP-G2 cells, which are well differentiated, showed marked degrees of enhancement of trans-activation after treatment with 12-O-tetradecanoylphorbol-13-acetate, SK-HEP-1 cells, which are poorly differentiated, showed only moderate or low degrees of enhancement. These two cell lines up-regulated their trans-activating activities in response to the deletion of some regions of positive and negative regulatory elements, suggesting that they produce trans-acting factors that are quantitatively different from each other, and often employ different sets of positive and negative regulatory elements for trans-activation.

Base Sequence↗

PubMed1993

Detection of the AML1/ETO fusion transcript in the t(8;21) masked translocation in acute myelogenous leukemia.

The fusion transcript AML1/ETO was detected in the bone marrow of two t(8;21)-negative acute myelogenous leukemia (AML) patients by means of reverse transcription-polymerase chain reaction. This fusion transcript is identical to the one transcribed from the t(8;21) translocation base, as deduced from (a) the size and restriction pattern of the amplified DNA fragment and (b) the DNA sequence analysis of the fusion junction. We also showed that the ETO gene is highly expressed in these patients, much as it is in the t(8;21)-positive AML. Southern blot analysis showed rearrangement of the AML1 gene in one of the patients. Together, our results demonstrate that there is a masked t(8;21) translocation in AML that is not detectable by cytogenetic analysis but is able to transcribe an AML1/ETO fusion transcript similar to that transcribed in t(8;21)-positive AML-M2 patients.

Base Sequence↗