Acute myeloid leukemias with ring sideroblasts show a unique molecular signature straddling secondary acute myeloid leukemia and de novo acute myeloid leukemia
Acute myeloid leukemias with ring sideroblasts show a unique molecular signature straddling secondary acute myeloid leukemia and de novo acute myeloid leukemia
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具有环状铁粒幼细胞的急性髓系白血病显示出跨继发性急性髓系白血病和新发急性髓系白血病的独特分子特征
DOI：
10.3324/haematol.2016.156844
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发表时间：
2017
期刊：
影响因子：
10.1
通讯作者：
T. Haferlach
中科院分区：
文献类型：
--
作者：
P. Martin;S. Jeromin;K. Perglerová;C. Haferlach;W. Kern;T. Haferlach
环形铁粒幼细胞（RS）是骨髓增生异常综合征（MDS）、骨髓增生异常/骨髓增生性肿瘤（MDS/MPN）和急性髓性白血病（AML）中存在的独特形态学特征。骨髓增生异常综合征形态学国际工作组（IWGM-MDS）将其定义为具有至少5个含铁颗粒覆盖至少三分之一核周长的成红细胞。在64-83%的难治性贫血伴环形铁粒幼细胞（RARS）患者、57-76%的难治性血细胞减少伴多系发育不良和环形铁粒幼细胞（RCMD-RS）患者和90%的RARS伴血小板增多（RARS-T）患者中，其≥15%的存在与剪接因子3B亚基1（SF 3B 1）突变相关。最近，2016年修订的世界卫生组织（WHO）髓系肿瘤和急性白血病分类已经认识到SF 3B 1 mut的生物学重要性及其与RS的相关性，将所有没有过量原始细胞或5 q缺失的MDS分类为自己的类别。SF 3B 1突变频繁与RS相关，因此如果证实了SF 3B 1突变，则MDS可被分类为携带RS的阈值已从经典的15%降低至5%。虽然SF 3B 1突变的影响最初与MDS的更好结局相关，但这可以通过低级别MDS的发病率较高以及突变本身缺乏预后意义来解释。最近的研究表明，SF 3B 1在初发AML中的发生率较低。然而，RS和SF 3B 1 mut在AML中的意义尚未在更大的队列中评估。为了分析RS是否可以区分具有不同生物学特征的AML亚组，我们在此介绍了AML患者（n=1857）中RS和SF 3B 1突变的生物学和临床相关性。共1857例AML患者（不包括WHO确定的细胞遗传学实体），骨髓评估显示473例（25%）RS ≥ 1%，其中290例（所有1857例患者中的16%）RS ≥ 5%，183例（所有1857例患者中的10%）的RS ≥15%，表明RS的发生率低于文献中描述的MDS患者队列（57%的病例显示RS ≥1%）。然而，这一发生率显著高于最近在AML患者中报告的发生率（5%）。然而，必须承认，特别是在RS计数较低的病例中，不能排除RS的其他原因，如饮酒或药物毒性。在473名患者中的340名患者的子队列中（由于样本可用性）进行了全髓系组的下一代测序（NGS）、基因扫描和定量聚合酶链反应（PCR），以检测
Ring sideroblasts (RS) are a distinct morphological feature present in myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and acute myeloid leukemia (AML). The International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) defines them as erythroblasts with a minimum of 5 siderotic granules covering at least one third of the circumference of the nucleus. Their presence ≥15% has been associated with mutations in the splicing factor 3B subunit 1 (SF3B1) in 64-83% of patients with refractory anemia with ring sideroblasts (RARS), 57-76% of patients with refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) and in 90% of RARS with thrombocytosis (RARS-T). Recently, the 2016 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemias has recognized the biological importance of SF3B1mut and the correlation with RS, classifying all MDS without excess blasts or 5q deletion into a category of their own. Mutations in SF3B1 are so frequently associated with RS that the threshold at which MDS may be classified as bearing RS has been lowered from the classical 15% to 5% if SF3B1 mutations are demonstrated. Although the impact of SF3B1 mutations was initially associated with better outcomes in MDS, this can be explained through a higher incidence in low-grade MDS and due to the lack of prognostic significance carried by the mutation itself. Recent studies have shown the incidence of SF3B1 in de novo AML is low. However the significance of RS and SF3B1mut in AML had not been assessed in a larger cohort. In an attempt to analyze whether RS could differentiate a subgroup of AML with different biological characteristics, we herein present the biological and clinical associations of RS and SF3B1 mutations in patients with AML (n=1857). From a total of 1857 AML patients (excluding those with cytogenetically defined entities according to WHO), bone marrow assessment revealed 473 (25%) with RS ≥1%, of which 290 (16% of all 1857 patients) had RS ≥5%, and 183 (10% of all 1857 patients) had ≥15% RS, indicating a lower incidence of RS in comparison to cohorts of MDS patients described in the literature (57% of cases showing RS ≥1%). This incidence was, however, significantly higher to that recently reported in AML patients (5%). It must be acknowledged, however, that especially in those cases with lower RS counts, other causes of RS, like alcohol consumption or drug toxicity, cannot be excluded. Next-generation sequencing (NGS) for a panmyeloid panel, gene scan and quantitative polymerase chain reaction (PCR) were performed in a subcohort of 340/473 patients (due to sample availability) for the detection of
影响因子：
20.3
作者：
Lindsley, R. Coleman;Mar, Brenton G.;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
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
DOI：
10.1056/nejmoa1516192
发表时间：
2016-06-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Papaemmanuil E;Gerstung M;Bullinger L;Gaidzik VI;Paschka P;Roberts ND;Potter NE;Heuser M;Thol F;Bolli N;Gundem G;Van Loo P;Martincorena I;Ganly P;Mudie L;McLaren S;O'Meara S;Raine K;Jones DR;Teague JW;Butler AP;Greaves MF;Ganser A;Döhner K;Schlenk RF;Döhner H;Campbell PJ
通讯作者：
Campbell PJ