Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia.
Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia.
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DOI：
10.1182/bloodadvances.2023009675
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发表时间：
2023-09-12
期刊：
影响因子：
7.5
通讯作者：
Xiao, Wenbin
中科院分区：
文献类型：
--
作者：
Mccarter, Joseph G. W.;Nemirovsky, David;Famulare, Christopher A.;Farnoud, Noushin;Mohanty, Abhinita S.;Stone-Molloy, Zoe S.;Chervin, Jordan;Ball, Brian J.;Epstein-Peterson, Zachary D.;Arcila, Maria E.;Stonestrom, Aaron J.;Dunbar, Andrew;Cai, Sheng F.;Glass, Jacob L.;Geyer, Mark B.;Rampal, Raajit K.;Berman, Ellin;Abdel-Wahab, Omar I.;Stein, Eytan M.;Tallman, Martin S.;Levine, Ross L.;Goldberg, Aaron D.;Papaemmanuil, Elli;Zhang, Yanming;Roshal, Mikhail;Derkach, Andriy;Xiao, Wenbin
个体发生分配从数据库登记缺乏敏感性和特异性。个体发生对MR基因突变AML的结局进行分层。准确的分类和危险分层是急性髓细胞白血病（AML）患者临床决策的关键。在新提出的世界卫生组织和国际共识的血液淋巴样肿瘤分类中，骨髓增生异常相关（MR）基因突变的存在被列为AML（AML-MR）的诊断标准之一，主要基于这些突变对伴有既往骨髓增生异常综合征的AML具有特异性的假设。ICC还将MR基因突变优先于个体发育（如临床病史中所定义）。此外，欧洲白血病网（ELN）2022将这些MR基因突变分为不良风险组。通过对纪念斯隆-凯特琳癌症中心344例新诊断的AML患者进行全面注释，我们发现基于数据库登记的个体发育分配缺乏准确性。MR基因突变常在初治AML中观察到。在MR基因突变中，只有EZH 2和SF 3B 1在单变量分析中与较差的结果相关。在多变量分析中，AML个体发生具有独立的预后价值，即使在调整了年龄、治疗、同种异体移植和基因组分类或ELN风险后。个体发生也有助于分层的结果与MR基因突变的AML。最后，MR基因突变的初治AML未显示不良结局。总之，我们的研究强调了在临床研究中准确的个体发育指定的重要性，证明了AML个体发育的独立预后价值，并质疑了MR基因突变AML的当前分类和风险分层。
Ontogeny assignment from the database registry lacks sensitivity and specificity. Ontogeny stratifies the outcome of AML with MR gene mutations. Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization and International Consensus classifications of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as 1 of the diagnostic criteria for AML, AML-MR, based largely on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined in the clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations into the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed patients with AML treated at the Memorial Sloan Kettering Cancer Center, we show that ontogeny assignments based on the database registry lack accuracy. MR gene mutations are frequently observed in de novo AML. Among the MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in the univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also helped stratify the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny, and questions the current classification and risk stratification of AML with MR gene mutations.
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影响因子：
28.2
作者：
Daver, Naval G.;Maiti, Abhishek;Kadia, Tapan M.;Vyas, Paresh;Majeti, Ravindra;Wei, Andrew H.;Garcia-Manero, Guillermo;Craddock, Charles;Sallman, David A.;Kantarjian, Hagop M.
通讯作者：
Kantarjian, Hagop M.
影响因子：
20.3
作者：
Lindsley, R. Coleman;Mar, Brenton G.;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
10.1
作者：
Caprioli C;Lussana F;Salmoiraghi S;Cavagna R;Buklijas K;Elidi L;Zanghi' P;Michelato A;Delaini F;Oldani E;Intermesoli T;Grassi A;Gianfaldoni G;Mannelli F;Ferrero D;Audisio E;Terruzzi E;De Paoli L;Cattaneo C;Borlenghi E;Cavattoni I;Tajana M;Scattolin AM;Mattei D;Corradini P;Campiotti L;Ciceri F;Bernardi M;Todisco E;Cortelezzi A;Falini B;Pavoni C;Bassan R;Spinelli O;Rambaldi A
通讯作者：
Rambaldi A
影响因子：
45.3
作者：
Haferlach, T;Schoch, C;Hiddemann, W
通讯作者：
Hiddemann, W