The frequency of nonhemagglutinating (h-) mutants was determined in hemagglutinating (HA) clones of echovirus 11. The HA clones were derived from the prototype strain Gregory and a clinical isolate of echovirus 11. The h- mutants were found at a constant frequency of 3.0 x 10(-5) (mean value) in the HA clones derived from both strains. Since the conditions of the population equilibrium of HA clones and neutrality of the mutation were satisfied, it was proposed that the observed frequency of h- mutants occurred as a result of a point mutation. The frequency of h+ revertants at the second passage of h- mutant clone was 9.1 x 10(-5). Hence the frequency of reversion suggests that the number of potential sites of back mutation was restricted.
1 sverdlovsk regional ministry of health, ekaterinburg, russian federation 2 ural state medical university, ekaterinburg, russian federation 3 institute of medical cell Technology, ekaterinburg, russian federation 4 stavropol state medical university, russian federation 5 regional clinical oncology center, stavropol, russian federation В исследование включены образцы костного мозга и периферической крови 77 больных с впервые выявленным ОМЛ с созреванием (М2 по FAB-классификации), в том числе 20 в возрасте 17-44 лет, 24 в возрасте 46-60 лет, 33 в возрасте старше 60 лет в период 2008-2020 гг. Детекцию хромосомных мутаций проводили с использованием стандартного цитогенетического метода (G-бэндинг) и полимеразной цепной реакции в режиме реального времени. Исследовали мутации в генах ASXL1 (экзоны 12-13), c-KIT (экзоны 7-12 и 16-19), DNMT3A (экзоны 18-26), FLT3 (экзоны 12-15 и 19-21), KRAS (экзоны 1-4), NPM1 (экзоны 9-12), NRAS (экзоны 1-4), TP53 (экзоны 4-11) и WT1 (экзоны 6-9) методом прямого автоматического секвенирования мРНК.Общая частота генных мутаций при ОМЛ М2 составила 37,7 %, при этом наиболее часто мутации определялись в генах FLT3 (14,5 %), NRAS (14,0 %), TP53 (11,3 %), ASXL1 (10,0 %), NPM1 (8,2 %). Мутации в гене KRAS выявлены не были, что может быть обусловлено объемом выборки. Частота двойных мутаций в указанных генах при ОМЛ M2 составила 7,9 %, среднее число мутаций на образец -1,2, при этом наиболее часто кооперировались мутации в генах FLT3 и NPM1. Средний возраст пациентов с лейкозными клетками, несущими мутации в генах ASXL1, c-KIT, FLT3, NPM1, NRAS и WT1, соответствовал зрелому возрасту, ТP53 -пожилому, DNMT3A -старческому. Средний возраст больных ОМЛ М2 с двумя генными мутациями также соответствовал пожилому возрасту. Ключевые слова: острый миелобластный лейкоз с созреванием, хромосомные аберрации, генные мутации, прямое секвенирование, возрастBone marrow and peripheral blood samples were examined in 77 patients (pts) with de novo AML with maturation (M2 according to FAB classification), including 20 pts aged 17-44, 24 pts aged 46-60, 33 pts aged over 60 years in the period 2008-2020. Detection of chromosomal mutations was performed using the standard cytogenetic method (G-banding) and real-time polymerase chain reaction. Mutations in the genes ASXL1 (exons 12-13), c-KIT (exons 7-12 and 16-19), DNMT3A (exons 18-26), FLT3 (exons 12-15 and 19-21), KRAS (exons 1-4), NPM1 (exons 9-12), NRAS (exons 1-4), TP53 (exons 4-11), and WT1 (exons 6-9) were studied by direct automatic mRNA-sequencing.The overall frequency of gene mutations in AML M2 was 37.7%, with the most common mutations being identified in the FLT3 (14.5 %), NRAS (14.0 %), TP53 (11.3 %), ASXL1 (10.0 %) and NPM1 (8.2 %) genes. Mutations in the KRAS gene were not detected, which may be due to the sample size. The frequency of double mutations in AML M2 samples was 7.9 %, the average number of mutations per specimen was 1.2, and mutations in the FLT3 and NPM1 genes were most often cooperated. The average age of pts with leukemia cells carryin...
The frequency of acute myeloid leukemia (AML) increases with age, respectively, the range of identified gene mutations and the pathways involved carcinogenesis can vary and affect the prognosis of treatment. The aim of the study was to estimate the frequency of mutations in DNMT3A, FLT3, KIT, NPM1, NRAS, TP53 and WT1 genes in acute myeloid leukemia (AML) patients (pts) aged 15-45 years old using direct automatic sequencing technique. Bone marrow and peripheral blood samples obtained from 36 AML pts aged 15 to 45. Distribution of the pts according to FAB-classification was as follows: AML M0 - 2, M1 - 1, M2 - 15, М3 - 2, M4 - 11, M4eo - 2, M5 - 2, blastic plasmacytoid dendritic cell neoplasm-1. Detection of mutations in ASXL1, DNMT3A, FLT3, KIT, NPM1, NRAS, TP53 and WT1 genes performed by automatic direct sequencing technique. The average frequency of functionally significant mutations in all investigated genes among the treated AML pts was 41,7 % (n=15), including 6 cases (40,0 %) with unfavorable cytogenetics, 6 cases (54,5 %) with normal karyotype, 3 cases (37,5 %) with favorable cytogenetics. These data correspond to the average frequency of point mutation in AML with normal and abnormal karyotype. Average frequency of mutations in FLT3 gene exons 12-15 and 19-21 - 21,9 %, NRAS gene exons 1-4 - 13,0 %, WT1 gene exons 6-9 - 11,1%, NPM1 gene exons 9-12 was 10,7 %, KIT gene exons 7-12 and 16-19 - 10,0 %, DNMT3A exons 18-26 - 7,1 %, TP53 gene exons 4-11 - 0,0 %. Multiple point mutations in investigated genes detected in 13.9 % AML specimens (usually KIT gene non-synonymous substitution c. 1621 А>С). Cryptic gene mutations detection using direct sequencing technique allowed to clarify the prognostic stratification of AML from groups of favorable and intermediate prognosis in 36,8 % (n=7). Thus, using of cytogenetic and additional molecular genetic research, a favorable prognosis of overall survival was established in 6 cases (16,7 %), intermediate - in 10 cases (27,8 %), adverse - in 18 cases (50,0 %), and unspecified - in 2 (5,6 %).
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