Expression of the gene Wilms tumor 1 (WT1) has been suggested as a marker of minimal residual disease in acute myeloid leukemia (AML), but literature data are not without controversy. Our aim was to assess the presence, magnitude and temporal changes of WT1 expression as prognostic factors. 60 AML patients were followed until death or the end of the 6-year observation period. Blood samples were taken at diagnosis, post-induction, during remission and in case of a relapse. Using quantitative real-time PCR, we determined WT1 expression from each sample, normalized it against the endogenous control gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and classified samples as negative, moderately positive or highly positive. We divided the patients into groups based on detected WT1 expression values, illustrated overall and disease-free survival on Kaplan-Meier curves, and compared differences between each group by the logrank test. Disappearance of WT1-positivity during chemotherapy had a favorable effect on survival. Interestingly, no difference was seen between the survivals of WT1-positive subgroups that expressed moderate or high levels of WT1 mRNA. A 1-log decrease in WT1 expression without becoming negative did not affect prognosis, either. Our results suggest that defining a cut-off value for WT1-positivity, rather than just using logarithmic figures of changes in gene expression, might have prognostic use in post-induction AML patients. We encourage further, larger-scale studies.
Abstract:The Wilms tumor 1 (WT1) gene has a complex role as a transcriptional regulator, acting as tumor suppressor or oncogene in different malignancies. The prognostic role of its overexpression has been well-studied in leukemias, especially acute myeloid leukemia (AML), but not in lymphomas. For the first time to our knowledge, we present a study demonstrating the correlation of WT1 expression and survival in various non-Hodgkin lymphomas. We also studied the prognostic implications of WT1 overexpression in adult acute lymphoblastic leukemia (ALL). In our sample of 53 patients -25 with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), 9 with peripheral T-cell lymphoma (PTCL), 2 with Burkitt's lymphoma, 2 with mucosa-associated lymphoid tissue (MALT) lymphoma, and 7 with B-cell ALL -, we measured WT1 mRNA from blood samples by quantitative RT-PCR, and divided the patients into subgroups based on the level of expression. Kaplan-Meier survival curves were drawn and compared using the logrank test. In the sample of DLBCL patients, the difference in overall and disease-free survival between WT1-positive and negative subgroups was significant (p=0,0475 and p=0,0004, respectively), and in a few observed cases, a sudden increase in WT1 expression signified a relapse soon followed by death. Disease-free survival curves in MCL and ALL were similarly suggestive of a potential role played by WT1. In PTCL, though WT1-positivity was detected in 4 out of 9 cases, it did not seem to affect survival. The few cases of MALT and Burkitt's lymphoma all proved to be WT1-negative.
The main goal of our research was to study the effects of different feed components and the treatment of the litter on the NH3 emission of equine urine. Four adult horses were used in the experiment. The basic diet consisted of 1500 g mashed oat, fed twice a day (morning and evening), and ad libitum hay. During the night the horses were kept separately in concrete floor boxes, the litter was wheat straw. The whole study was divided into 3 main periods. In the first period of the experiment the litter and the floor were treated with a probiotic supplement for two days in the evenings. In the second period of the experiment for 8 days the basic diet was supplemented with 40 ml of probiotic added to the oat. Before the third period of our study the horses were fed with their regular diet for two weeks. After that the oat was changed to a high-protein-value horse feed for 12 days. At the end of the second and third periods, the litter was treated again. Urine contaminated straw samples were collected after each period before and after the litter treatments from different places of the litter in the morning before the daily littering. From the samples, the dry matter content and the NH3 emission were measured. Statistical analysis was carried out with linear modelling. According to our results, both the probiotic treatment of the feed and the high-protein-value horse feed decreased the urine NH3 emission significantly (p<0.05). However, the NH3 emission was only slightly influenced by the litter treatment. Only in the case of probiotic feed supplement could a decrease in emission be detected, but the result was not significant. There was no difference in the dry matter content of the samples. Based on our results, we can conclude that both the high-protein-value horse feed and the probiotic supplement applied in our experiment can be useful to decrease urine NH3 emission by horses. The two-days litter treatment however seems to be too short to gain any positive effects.
An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function.
Az akut myeloid leukaemia heterogén betegség. A mutációs vizsgálatoknak köszönhetően genetikailag és molekulá-risan is jellemezhető típusok váltak ismertté. Kezelése -az akut promyelocytás leukaemia kivételével -egyforma. Kezelésében több mint 40 éve a "3 + 7" protokoll a meghatározó. Míg a cytarabin dózisa az eltelt idő során nem változott, a daunorubicin adagjának növelése (90 mg/m 2 ) a 60-65 év alatti, jó állapotú betegekben javította a túl-élést. A 60 évnél idősebbek azonban az intenzív kemoterápiát általában rosszul tolerálják. Időskorban a kezelés nem kuratív, a cél a hosszabb túlélés és a megfelelő életminőség biztosítása. A szupportív kezelés mellett újabban a kis intenzitású terápia (azacitidin, decitabin) kerül előtérbe. Az innovatív terápiától a jövőben további javulás remélhető. Orv. Hetil., 2016, 157(22), 843-848.Kulcsszavak: akut myeloid leukaemia, génmutációk, "3 + 7" protokoll, nagy dózisú daunorubicin, decitabin, azacitidin, innovatív terápia Drug treatment of acute myelogenous leukaemia Current options and future perspectivesAcute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the "3 + 7" induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m 2 had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia.
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