Clonal trajectories and cellular dynamics of myeloid neoplasms with SF3B1 mutations.
Clonal trajectories and cellular dynamics of myeloid neoplasms with SF3B1 mutations.
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具有SF3B1突变的髓样肿瘤的克隆轨迹和细胞动力学。
DOI：
10.1038/s41375-021-01176-7
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发表时间：
2021-11
期刊：
影响因子：
11.4
通讯作者：
Visconte V
中科院分区：
文献类型：
--
作者：
Awada H;Kerr CM;Durmaz A;Adema V;Gurnari C;Pagliuca S;Zawit M;Kongkiatkamon S;Rogers HJ;Saunthararajah Y;Sekeres MA;Carraway H;Maciejewski JP;Visconte V
分子损伤，无论是结构性细胞遗传学异常还是已知意义的基因突变，都是以循序渐进的方式发生的，是髓系肿瘤(MN)的形态和预后标志。目前世界卫生组织的分类将具有≥15%的环状铁粒母细胞(RS)的骨髓增生异常综合征(MDS)患者或具有SF3B1突变的≥5%RS的患者归类为MDS-RS[1]，这是一种存在SF3B1突变的亚型[2-6]。虽然大多数SF3B1MT患者具有典型的表型，但在这一亚型中存在相当大的异质性，包括最初有利的临床表型的个体转移。在MNS的病程中可以观察到RS的消失，提示新的细胞移位可能伴随着向急性髓系白血病(AML)的演变而发生。这些过程可能是SF3B1MT的类型和配置的结果，这可能会影响疾病的进程。受到一项开创性工作的启发，该工作将SF3B1MT描述为一种定义疾病的分子损伤，其存活率和克隆进化的独立风险[6]，我们仔细观察了我们的初步观察，表明重要的生物学线索可以从SF3B1MT的分子关联及其克隆结构在MNS的背景下推断[7]。为此，我们回顾了MNS患者的临床和分子注释，目的是解剖SF3B1突变组，并描述克隆等级(祖先/显性与亚克隆/次级)是否会改变表型细胞的轨迹。我们在大约6%的MN患者(209/3673)中发现了209例SF3B1MT。队列的临床和分子数据在克利夫兰临床基金会收集，并从公开可用的数据集中检索(请参阅补充材料)以供比较。人口学、临床和细胞遗传学特征汇总于表S1。使用之前由PyClone方法[7，8]证实的变异等位基因频率(VAF)估计，SF3B1MT被分类为：(I)显性(SF3B1DOM，n=96，46%)，(Ii)次要(SF3B1Sec，n=68，33%)。正如预期的那样，由于缺乏所采用的生物信息学方法的解决方案，亚类分类包括(Iii)“共显性”的过渡类别(SF3B1COD，n=45，21%)。图1A描述了这些配置的示意图，尽管对于其他并发突变有不同的等级分配，但3组中的SF3B1MT VAFs在统计上没有差异
Molecular lesions, either structural cytogenetic anomalies or gene mutations of known significance, occur in a stepwise fashion and are morphologic and prognostic markers in myeloid neoplasms (MNs). Current World Health Organization (WHO) classification categorizes patients with myelodysplastic syndrome (MDS) with ringed sideroblasts (RS)≥ 15% or≥ 5% RS with an SF3B1 mutation (SF3B1MT) as MDS-RS [1], a subtype in which the presence of SF3B1 mutations confers a favorable prognosis [2–6]. Although most patients with SF3B1MT have a classic phenotype, there is considerable heterogeneity within this subcategory including individual diversion of the originally favorable clinical phenotype. The disappearance of RS can be observed during the disease course of MNs, suggesting that new cellular shifts, due to the acquisition of additional lesions cooperating with/or suppressing SF3B1MT might go along with evolution to acute myeloid leukemia (AML). Such courses are likely a result of the type and configuration of SF3B1MT, which potentially impact the disease course.Inspired by a seminal work describing SF3B1MT as a disease-defining molecular lesion in terms of survival and independent risk of clonal evolution [6], we looked closer at our preliminary observations suggesting that important biological clues can be extrapolated from the molecular associations of SF3B1MT and their clonal architecture in the context of MNs [7]. To that end, we reviewed clinical and molecular annotations of patients with MNs with the intent of dissecting the SF3B1 mutatome and describing whether the clonal rank (ancestral/dominant vs. sub-clonal/secondary) might alter the phenotypic cell trajectories. We identified 209 SF3B1MT in about 6% of MN patients (209/3673). Clinical and molecular data of the cohort were collected at The Cleveland Clinic Foundation and retrieved from publicly available datasets (refer to Supplementary Material) for comparisons’ purposes. The demographic, clinical and cytogenetic characteristics are summarized in Table S1. Using variant allele frequencies (VAFs) estimation that was previously confirmed by PyClone method [7, 8], SF3B1MT were categorized as:(i) dominant (SF3B1DOM, n= 96, 46%),(ii) secondary (SF3B1SEC, n= 68, 33%) and as expected, due to the lack of resolution of the bioinformatics methods deployed, sub-categorization included transitional category of (iii)“co-dominant”(SF3B1COD, n= 45, 21%). Schematic representations of these configurations are described in Fig. 1 A. Despite the different hierarchical assignments with respect to other concurrent mutations, SF3B1MT VAFs in the 3 groups did not statistically vary
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影响因子：
50.3
作者：
Obeng EA;Chappell RJ;Seiler M;Chen MC;Campagna DR;Schmidt PJ;Schneider RK;Lord AM;Wang L;Gambe RG;McConkey ME;Ali AM;Raza A;Yu L;Buonamici S;Smith PG;Mullally A;Wu CJ;Fleming MD;Ebert BL
通讯作者：
Ebert BL
DOI：
10.1056/nejmoa1103283
发表时间：
2011-10-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Papaemmanuil E;Cazzola M;Boultwood J;Malcovati L;Vyas P;Bowen D;Pellagatti A;Wainscoat JS;Hellstrom-Lindberg E;Gambacorti-Passerini C;Godfrey AL;Rapado I;Cvejic A;Rance R;McGee C;Ellis P;Mudie LJ;Stephens PJ;McLaren S;Massie CE;Tarpey PS;Varela I;Nik-Zainal S;Davies HR;Shlien A;Jones D;Raine K;Hinton J;Butler AP;Teague JW;Baxter EJ;Score J;Galli A;Della Porta MG;Travaglino E;Groves M;Tauro S;Munshi NC;Anderson KC;El-Naggar A;Fischer A;Mustonen V;Warren AJ;Cross NC;Green AR;Futreal PA;Stratton MR;Campbell PJ;Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
通讯作者：
Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
影响因子：
64.5
作者：
Xu, XD;Yang, DM;Fu, XD
通讯作者：
Fu, XD
影响因子：
20.3
作者：
Malcovati, Luca;Stevenson, Kristen;Cazzola, Mario
通讯作者：
Cazzola, Mario
影响因子：
20.3
作者：
Taylor, Justin;Mi, Xiaoli;Abdel-Wahab, Omar
通讯作者：
Abdel-Wahab, Omar