genetic characteristics

遗传特征
  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fgene.2024.1395988。].
    [This corrects the article DOI: 10.3389/fgene.2024.1395988.].
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  • 文章类型: Journal Article
    手,口蹄疫(HFMD)是过去几十年来最常见的传染病之一。2013年后,柯萨奇病毒A6(CVA6)取代了肠道病毒71(EV-A71)和柯萨奇病毒A16(CVA16),在中国许多地区已成为手足口病的主要病原。本研究的目的是调查2022-2023年临沂市CVA6的遗传特征和分子流行病学。本研究共纳入965例HFMD病例,并基于VP1核苷酸序列进行分析以确定CVA6的进化轨迹。2022年,281例(281/386,72.8%)肠道病毒(EV)阳性,CVA6阳性217例(217/281,77.2%)。2023年,398个(398/579,68.7%)样本为电动汽车阳性,CVA6阳性243例(243/398,61.1%)。每年选择6个序列进行同源性分析。结果表明,临沂分离的12株菌株与原型菌株(AY421764)和中国报道的第一株CVA6菌株(JQ364886)相去甚远。系统发育分析表明,临沂分离的CVA6菌株均属于D3亚型。CVA6是临沂手足口病的常见病原体,和连续监测手足口病的病因是必要的。
    Hand, foot and mouth disease (HFMD) was one of the most common infectious disease in the past few decades. After 2013, coxsackievirus A6 (CVA6) has replaced enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16), becoming the predominant pathogen responsible for HFMD in many areas in China. The objective of this study is to investigate the genetic characteristics and molecular epidemiology of CVA6 in Linyi from 2022 to 2023. A total of 965 HFMD cases were enrolled in this study and analyses based on VP1 nucleotide sequences were performed to determine the evolutionary trajectory of CVA6. In 2022, 281 (281/386, 72.8%) were positive for enterovirus (EVs), and 217 (217/281, 77.2%) were CVA6 positive. In 2023, 398 (398/579, 68.7%) samples were positive for EVs, and 243 (243/398, 61.1%) were CVA6 positive. Six sequences were selected from each year for the homology analysis. The results showed that 12 strains isolated in Linyi were far from the prototype strain (AY421764) and the first CVA6 strain reported in China (JQ364886). Phylogenetic analysis showed that the CVA6 strains isolated in Linyi all belonged to D3 subgenotype. CVA6 is emerging as a common pathogen causing HFMD in Linyi, and continuous surveillance of HFMD etiological agents is necessary.
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  • 文章类型: Journal Article
    先天性代谢错误(IEM)并不常见。尽管一些研究已经探讨了新生儿中IEM的分布和特征,这些疾病对住院新生儿的影响尚不清楚.在这项研究中,我们收集了2017年1月至2022年12月在重庆医科大学儿童医院因各种疾病入院的21,840名新生儿患者的数据。液相色谱-串联质谱(LC-MS/MS),气相色谱-质谱(GC-MS/MS),和遗传分析被用来阐明疾病谱,发病率,住院新生儿IEM的遗传特征。结果显示,住院新生儿中IEM的发生率为1/377(58/21,840),足月婴儿(1/428)的发病率高于早产儿(1/3,120)。在诊断的遗传代谢疾病中,有机酸代谢紊乱(1/662),氨基酸代谢紊乱(1/950),和脂肪酸氧化紊乱(1/10,920)是最普遍的。甲基丙二酸血症(MMA),尤其是孤立的形式,成为最常见的IEM,而由citrin缺乏症(NICCD)和鸟氨酸转碳淀粉酶缺乏症(OTCD)引起的新生儿肝内胆汁淤积在早产儿中普遍存在。在58例确诊的IEM病例中,确定了72种变体,其中31.94%(23/72)以前没有报告过。这项研究有助于了解住院新生儿IEM的发生率和临床特征,为筛查和诊断这些疾病提供更有效的策略。
    Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children\'s Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.
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  • 文章类型: Journal Article
    甘蔗,热带和亚热带地区的重要经济作物,贡献了世界上80%的糖产量和40%的生物乙醇产量。它是一种关键的糖料作物,占中国食糖产量的85%。开发高产新品种,高糖,良好的抗逆性对制糖行业的可持续增长至关重要。杂交育种是目前应用最广泛、最有效的方法,超过98%的中国甘蔗品种是由这种方法产生的。在过去的二十年里,我国育种家发展了高异质复合高糖育种理论,导致第五代甘蔗品种的成功选育。其中,YZ08-1609,糖果属的复杂杂种。,由云南省农业科学院甘蔗研究所(YSRI)开发。YZ08-1609的平均甘蔗产量比ROC22高14.4%。它对花叶病有很强的抵抗力,对干旱胁迫具有高度的耐受性,但中度易患黑穗病。值得注意的是,YZ08-1609的蔗糖含量为20.3%,创下国际纪录,赢得“糖之王”的美誉。总结经验,启发育种,我们在这里提供了父母选择的详细见解,育种过程,和YZ08-1609的特点。此外,在转录和代谢水平上都挖掘了其高产和高糖的生物学机制。还讨论了甘蔗品种选育的挑战和前景,尤其是高糖甘蔗品种的选育。为高糖品种的未来发展奠定了基础。
    Sugarcane, a significant cash crop in tropical and subtropical regions, contributes to 80% of sugar production and 40% of bioethanol production in the world. It is a key sugar crop, accounting for 85% of sugar production in China. Developing new varieties with high yield, high sugar, and better stress resistance is crucial for the sustainable growth of sugar industry. Hybrid breeding is the most widely used and effective method, with over 98% of Chinese sugarcane varieties resulting from this approach. Over the past two decades, Chinese breeders have developed the theory of high-heterogeneous composite high-sugar breeding, leading to the successful breeding of the fifth-generation sugarcane varieties. Among them, YZ08-1609, a complex hybrid of Saccharum spp., was developed by Sugarcane Research Institute (YSRI) of Yunnan Academy of Agricultural Sciences. The average cane yield of YZ08-1609 was 14.4% higher than ROC22. It is highly resistant to mosaic disease, and highly tolerant to drought stress, but moderately susceptible to smut disease. Notably, YZ08-1609 stands out with a sucrose content of 20.3%, setting an international record, earning the reputation as \"King of Sugar\". To summarize experience and inspire breeding, we provided here the detailed insights into the selection of parents, breeding process, and characteristics of YZ08-1609. Besides, the biological mechanisms underlying its high yield and high sugar was excavated at both transcriptional and metabolic levels. The challenges and prospects in breeding sugarcane varieties especially with high sugar were also discussed, offering a foundation for the future development of high-sugar varieties.
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  • 文章类型: Journal Article
    化生性乳腺癌是一种罕见的,侵略性,和化疗耐药的乳腺癌亚型,占不到1%的浸润性乳腺癌,以腺癌与梭形细胞为特征,鳞状上皮,和/或间充质组织分化。大多数化生乳腺癌表现出三阴性乳腺癌的特征,并且预后不良,生存率较低。这种亚型通常在PI3K/AKT途径中显示基因改变,Wnt/β-catenin通路,和细胞周期失调,并证明上皮-间质转化,免疫反应的变化,TP53突变,EGFR扩增,等等。目前,化生性乳腺癌的最佳治疗仍不确定.本文对其临床特征进行了全面的综述,分子特征,侵袭和转移模式,和化生性乳腺癌的预后,以及治疗策略的最新进展。
    Metaplastic breast cancer is a rare, aggressive, and chemotherapy-resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple-negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/β-catenin pathway, and cell cycle dysregulation and demonstrates epithelial-mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.
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  • 文章类型: Journal Article
    背景:比较正常新生儿和遗传代谢疾病高危儿童之间的差异。疾病概况包括氨基酸血症,脂肪酸氧化紊乱,和有机酸血症。
    方法:收集2010年12月至2020年12月上海高危人群新生儿和儿童的数据。
    结果:对232,561名新生儿进行了器质性疾病筛查,氨基酸,和脂肪酸代谢。初始阳性率为0.66%(1,526/232,561),阳性召回率为77.85%。阳性预测值为4.71%。其中,56例诊断为代谢异常。总发病率为1:4153。高苯丙氨酸血症和短链酰基辅酶A脱氢酶是新生儿最常见的疾病。此外,在56名儿童中,39例(69.42%)通过基因测序诊断。已经观察到14个IEM中的一些热点突变,包括PAH基因c.728G>A,c.611A>G,和ACADS基因c。1031A>G,c.164C>T.总共筛选了49,860名有症状的患者,其中185例被诊断为IEM,检出率为0.37%。高危婴儿中最常见的诊断疾病是甲基丙二酸血症和高苯丙氨酸血症。
    结论:与新生儿筛查相比,通过串联质谱法诊断的先天性代谢错误的临床病例更多。疾病谱,患病率,正常新生儿和高危儿童的遗传特征有很大不同。
    BACKGROUND: Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias.
    METHODS: Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020.
    RESULTS: 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia.
    CONCLUSIONS: There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.
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  • 文章类型: Journal Article
    背景:隐孢子虫是全球儿童腹泻的高致病性寄生虫。这里,对温州市有或无腹泻患儿隐孢子虫的流行病学现状和遗传特征进行潜在来源追踪,中国。
    方法:共招募1032名儿童,其中684人腹泻,348人没有腹泻,温州育英儿童医院,中国。从每个参与者收集粪便样本,然后提取DNA,基因分型,以及隐孢子虫种类和亚型的分子鉴定。
    结果:1032名(2.1%)儿童中有22名感染了隐孢子虫。腹泻和无症状儿童占2.5%(17/684)和1.4%(5/348),分别。确定了四种隐孢子虫,包括C.parvum(68.2%;15/22),C.felis(13.6%;3/22),C.viatorum(9.1%;2/22),和C.baileyi(9.1%;2/22)。两种C.parvum亚型命名为IIdA19G1(n=14)和IInA10(n=1),还发现了一种C.felis(XIXa)和C.viatorum(XVaA3g)亚型。
    结论:这是首次在温州儿童中发现隐孢子虫的研究,中国,使用PCR。人畜共患parvum的鉴定,C.Felis,C.viatorum,它们的亚型表明隐孢子虫在儿童和动物之间潜在的跨物种传播。此外,儿童中C.baileyi的存在表明,该物种的宿主范围比以前认为的要大,并且具有感染人类的能力。
    BACKGROUND: Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea were investigated with tracking of potential sources in Wenzhou City, China.
    METHODS: A total of 1032 children were recruited, 684 of whom had diarrhea and 348 without, from Yuying Children\'s Hospital in Wenzhou, China. Samples of stool were collected from each participant, followed by extraction of DNA, genotyping, and molecular identification of Cryptosporidium species and subtypes.
    RESULTS: Twenty-two of the 1032 (2.1%) children were infected with Cryptosporidium spp. with 2.5% (17/684) and 1.4% (5/348) in diarrhoeic and asymptomatic children, respectively. Four Cryptosporidium species were identified, including C. parvum (68.2%; 15/22), C. felis (13.6%; 3/22), C. viatorum (9.1%; 2/22), and C. baileyi (9.1%; 2/22). Two C. parvum subtypes named IIdA19G1 (n = 14) and IInA10 (n = 1), and one each of C. felis (XIXa) and C. viatorum (XVaA3g) subtype was found as well.
    CONCLUSIONS: This is the first research that identified Cryptosporidium in children of Wenzhou, China, using PCR. Identification of zoonotic C. parvum, C. felis, C. viatorum, and their subtypes indicate potential cross-species transmission of Cryptosporidium between children and animals. Additionally, the presence of C. baileyi in children suggests that this species has a wider host range than previously believed and that it possesses the capacity to infect humans.
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  • 文章类型: Journal Article
    Blastocystis sp., a significant zoonotic parasite with a global distribution, was the focus of this study, which aimed to investigate its prevalence and genetic diversity among diarrheic and asymptomatic children in Wenzhou, China. We collected 1,032 fecal samples from Yuying Children\'s Hospital, Wenzhou, China, comprising 684 from children with diarrhea and 348 from asymptomatic children. Genomic DNA extracted from these samples was used to detect Blastocystis spp. by PCR, targeting the small subunit ribosomal RNA gene. Subsequently, a phylogenetic tree was constructed, applying the maximum likelihood method. Blastocystis spp. were detected in 67 (6.5%) of the fecal samples. The prevalence rate of Blastocystis spp. in diarrheic children (8.8%; 60/684) was significantly higher than that in asymptomatic children (2.0%; 7/348) (χ 2 = 17.3, p < 0.001). Sequence analysis of the SSU rRNA gene identified five known Blastocystis spp. subtypes, ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12), and ST7 (n = 3). ST1 and ST3 were present in both diarrheic and asymptomatic children, while ST2, ST4, and ST7 were exclusive to diarrheic children. Intra-subtype genetic polymorphisms were identified, comprising four variations in ST1 (ST1-1 to ST1-4), five in ST3 (ST3-1 to ST3-5), two in ST4 (ST4-1 and ST4-2), and two in ST7 (ST7-1 and ST7-2). Notably, ST1-2 to ST1-4, ST3-3 to ST3-5, and ST7-1 and ST7-2 represent newly identified variations. The composition and genetic characteristics of subtypes among children in this region suggest various sources of infection, including human-to-human and animal-to-human transmission.
    UNASSIGNED: Prévalence moléculaire et distribution des sous-types de Blastocystis spp. parmi les enfants diarrhéiques et asymptomatiques à Wenzhou, Province du Zhejiang, Chine.
    UNASSIGNED: Blastocystis sp., un parasite zoonotique important avec une distribution mondiale, était au centre de cette étude, qui visait à étudier sa prévalence et sa diversité génétique parmi les enfants diarrhéiques et asymptomatiques de Wenzhou, en Chine. Nous avons collecté 1 032 échantillons fécaux à l’hôpital pour enfants Yuying de Wenzhou, en Chine, dont 684 provenant d’enfants souffrant de diarrhée et 348 d’enfants asymptomatiques. L’ADN génomique extrait de ces échantillons a été utilisé pour détecter Blastocystis sp. par PCR, ciblant le gène de la petite sous-unité de l’ARN ribosomal. Par la suite, un arbre phylogénétique a été construit, en appliquant la méthode du maximum de vraisemblance. Blastocystis sp. a été détecté dans 67 (6,5 %) des échantillons fécaux. Le taux de prévalence de Blastocystis spp. chez les enfants diarrhéiques (8,8 % ; 60 / 684) était significativement plus élevé que chez les enfants asymptomatiques (2,0 % ; 7 / 348) (χ2 = 17,3, p < 0,001). L’analyse de la séquence du gène de l’ARNr SSU a identifié cinq sous-types de Blastocystis spp., ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12) et ST7 (n = 3). Les sous-types ST1 et ST3 étaient présents chez les enfants diarrhéiques et asymptomatiques, tandis que ST2, ST4 et ST7 étaient exclusifs aux enfants diarrhéiques. Des polymorphismes génétiques intra-sous-types ont été identifiés, comprenant quatre variations dans ST1 (ST1-1 à ST1-4), cinq dans ST3 (ST3-1 à ST3-5), deux dans ST4 (ST4-1 et ST4-2) et deux dans ST7 (ST7-1 et ST7-2). Notamment, ST1-2 à ST1-4, ST3-3 à ST3-5, ST7-1 et ST7-2 représentent des variations nouvellement identifiées. La composition et les caractéristiques génétiques des sous-types chez les enfants de cette région suggèrent diverses sources d’infection, notamment la transmission interhumaine et animale.
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  • 文章类型: Journal Article
    沙门氏菌中质粒介导的氟喹诺酮(FQ)抗性基因qnr的流行和传播被认为是全球严重的公共卫生问题。到目前为止,没有全面的大规模研究集中在从鸡中分离的沙门氏菌中qnr基因的流行和遗传特征。在这里,这项研究旨在调查患病率,抗菌素耐药性(AMR)模式,和来自养鸡场的鸡源qnr阳性沙门氏菌菌株的分子特征,屠宰场,2020-2021年中国12个省份的市场。qnr基因的总体患病率为21.13%(56/265),在市场上患病率最高(36.11%,26/72),其次是农场(17.95%,21/117),和屠宰场(10.53%,9/76)。只检测到qnrS和qnrB基因,qnrS基因的患病率(19.25%,51/265)高于qnrB基因(1.89%,5/265)。全基因组测序鉴定出37个不同的AMR基因和15个质粒复制子,喹诺酮耐药决定区最常见的突变是parC(T57S;91.49%,43/47)。同时,在47株qnr阳性沙门氏菌中发现了四种不同的qnrS和两种qnrB遗传环境。总的来说,21.28%(10/47)的菌株能够接合转移,都是qnrS1阳性菌株,其中大多数可转移质粒是IncHI2型(n=4)。总的来说,中国鸡的qnr阳性沙门菌流行及其携带多个抗性和毒力基因和可转移质粒是一个主要问题,要求对qnr阳性沙门氏菌进行持续监测,并制定控制其流行和传播的措施。重要沙门氏菌是一种常见的食源性病原体,每年在全世界造成155,000人死亡。氟喹诺酮类药物(FQs)在多个国家和地区被用作治疗沙门氏菌感染的一线药物。然而,从鸡中分离的沙门氏菌中FQ抗性基因qnr的出现和患病率的增加已经被广泛报道。深入了解鸡AMR基因的遗传机制可以导致制定预防措施,以控制和降低耐药性的风险。在这项研究中,我们鉴定了从中国不同地区的鸡中分离出的qnr阳性沙门氏菌及其AMR模式和全基因组特征,为进一步控制其流行和传播提供理论依据。
    The prevalence and dissemination of the plasmid-mediated fluoroquinolone (FQ) resistance gene qnr in Salmonella are considered serious public health concerns worldwide. So far, no comprehensive large-scale studies have focused on the prevalence and genetic characteristics of the qnr gene in Salmonella isolated from chickens. Herein, this study aimed to investigate the prevalence, antimicrobial resistance (AMR) patterns, and molecular characteristics of chicken-originated qnr-positive Salmonella strains from chicken farms, slaughterhouses, and markets in 12 provinces of China in 2020-2021. The overall prevalence of the qnr gene was 21.13% (56/265), with the highest prevalence in markets (36.11%, 26/72), followed in farms (17.95%, 21/117), and slaughterhouses (10.53%, 9/76). Only the qnrS and qnrB genes were detected, and the prevalence rate of the qnrS gene (19.25%, 51/265) was higher than that of the qnrB gene (1.89%, 5/265). Whole genome sequencing identified 37 distinct AMR genes and 15 plasmid replicons, and the most frequent mutation in quinolone resistance determining regions was parC (T57S; 91.49%, 43/47). Meanwhile, four different qnrS and two qnrB genetic environments were discovered among 47 qnr-positive Salmonella strains. In total, 21.28% (10/47) of the strains were capable of conjugative transfer, and all were qnrS1-positive strains, with the majority of transferable plasmids being IncHI2 types (n = 4). Overall, the prevalence of qnr-positive Salmonella strains from chickens in China and their carriage of multiple resistance and virulence genes and transferable plasmids is a major concern, which calls for continuous surveillance of qnr-positive Salmonella and the development of measures to control its prevalence and transmission.IMPORTANCESalmonella is a common foodborne pathogen responsible for 155,000 deaths annually worldwide. Fluoroquinolones (FQs) are used as first-line drugs for the treatment of Salmonella infections in several countries and regions. However, the emergence and increasing prevalence of the FQ-resistant gene qnr in Salmonella isolated from chickens have been widely reported. Gaining insight into the genetic mechanisms of AMR genes in chicken could lead to the development of preventive measures to control and reduce the risk of drug resistance. In this study, we identified qnr-positive Salmonellae isolated from chickens in different regions of China and their AMR patterns and genome-wide characteristics, providing a theoretical basis for further control of their prevalence and transmission.
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  • 文章类型: Journal Article
    背景:急性髓系白血病(AML)是一种异质性疾病,其异质性与治疗反应相关。尽管威尼托克(VEN)为基础的AML治疗取得了成功,FLT3突变对治疗效果的影响尚不清楚.我们旨在比较FLT3突变(FLT3mut)和FLT3野生型(FLT3wt)患者基于VEN的治疗的疗效,并确定FLT3mut患者疗效的预测因子。
    方法:本研究共纳入266例AML患者(127例新诊断[ND]和139例难治性/复发性[R/R])接受基于VEN的方案。进行了回顾性分析,比较FLT3mut和FLT3wt患者的治疗反应和总生存期(OS)。应用Logistic回归和Cox比例风险模型来检查结果的临床和遗传预测因子。
    结果:基于VEN的治疗的中位数为两个周期,对于NDAML队列,FLT3mut组的复合完全缓解率(CRc)与FLT3wt组相当(79.3%vs.61.2%,p=0.072)。对于R/RAML队列,FLT3mut组的CRc率低于FLT3wt组。中位随访时间为8.6个月(95%置信区间[CI],8.0-10),在两个队列的FLT3mut和FLT3wt组中观察到的中位OS接近(14.0vs.19.9个月,p=0.356;10.0与11.9个月,p=0.680)。对于NDAML队列,在FLT3mut患者中,MRD阳性和RNA剪接突变预测生存率较低(风险比[HR],10.3;95%CI:2.0-53.8;p=0.006;HR11.3;95%CI:1.2-109.3;p=0.036)。对于R/RAML队列,在FLT3mut患者中,不良ELN风险与不良反应相关(比值比[OR],0.2;95%CI:0.1-0.8;p=0.025),而NPM1共突变与优越的反应相关(57.1%;OR,6.7;95%CI:1.5-30.1;p=0.014)。CR/CRi预测更好的生存期(HR0.2;95%CI:0.1-0.8;p=0.029),而DNMT3A突变预测存活率较低(HR,4.6;95%CI:1.4-14.9;p=0.011)。
    结论:FLT3突变可能影响R/RAML患者对基于VEN的治疗的反应,但不影响NDAML患者。此外,临床和遗传特征可以预测FLT3mut患者接受VEN治疗的结局.
    BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease, and its heterogeneity is associated with treatment response. Despite the demonstrated success of venetoclax (VEN)-based therapy for AML, the effect of FLT3 mutations on the efficacy of the therapy is poorly understood. We aimed to compare the efficacy of VEN-based therapy between FLT3-mutated (FLT3mut ) and FLT3 wild-type (FLT3wt ) patients and identify the predictors of efficacy in FLT3mut patients.
    METHODS: A total of 266 AML patients (127 newly diagnosed [ND] and 139 refractory/relapsed [R/R]) receiving VEN-based regimens were enrolled in this study. A retrospective analysis was performed, and the treatment responses and overall survival (OS) of FLT3mut and FLT3wt patients were compared. Logistic regression and Cox proportional hazards model were applied to examine the clinical and genetic predictors of outcomes.
    RESULTS: With a median of two cycles of VEN-based therapy, for the ND AML cohort, the FLT3mut group had a comparable composite complete remission (CRc) rate with the FLT3wt group (79.3% vs. 61.2%, p = 0.072). For the R/R AML cohort, the FLT3mut group exhibited a lower CRc rate than the FLT3wt group. With a median follow-up of 8.6 months (95% confidence interval [CI], 8.0-10), the median OS observed in the FLT3mut and FLT3wt groups for both cohorts were close (14.0 vs. 19.9 months, p = 0.356; 10.0 vs. 11.9 months, p = 0.680). For the ND AML cohort, in FLT3mut patients, MRD-positive and RNA-splicing mutation predicted inferior survival (hazard ratio [HR], 10.3; 95% CI: 2.0-53.8; p = 0.006; HR 11.3; 95% CI: 1.2-109.3; p = 0.036, respectively). For the R/R AML cohort, in FLT3mut patients, adverse ELN risk was associated with an inferior response (odds ratio [OR], 0.2; 95% CI: 0.1-0.8; p = 0.025), whereas NPM1 co-mutation was associated with a superior response (57.1%; OR, 6.7; 95% CI: 1.5-30.1; p = 0.014). CR/CRi predicted a better survival (HR 0.2; 95% CI: 0.1-0.8; p = 0.029), while DNMT3A mutation predicted an inferior survival (HR, 4.6; 95% CI: 1.4-14.9; p = 0.011).
    CONCLUSIONS: FLT3 mutations may influence response to VEN-based therapy in R/R AML patients but not in ND AML patients. Furthermore, clinical and genetic characteristics could predict outcomes of FLT3mut patients receiving VEN-based therapy.
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