Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms
Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms
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TdT 大 B 细胞淋巴瘤的突变景观支持其与 B 淋巴母细胞肿瘤的区别
DOI：
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发表时间：
2021
影响因子：
5.6
通讯作者：
S. Swerdlow
中科院分区：
文献类型：
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作者：
Shweta Bhavsar;Yen‐Chun Liu;Sarah E. Gibson;E. Moore;S. Swerdlow
补充数字内容可在文本中找到。在目前的世界卫生组织分类中，末端脱氧核苷酸转移酶（TdT）在高级别/大细胞B细胞淋巴瘤（LBCL）中的表达表明B淋巴母细胞淋巴瘤/白血病（B-LBL），尽管有报道称TdT在成熟LBCL或成熟B细胞肿瘤中表达。TdT+ LBCL的发生率、如何最好地对这些病例进行分类、其临床病理特征、分子特征以及与经典B-LBL的关系仍有待更好地确定。因此，在258例LBCL中评估了TdT表达，结果与细胞学、表型和细胞遗传学结果相关。在6例TdT+细胞>10%的病例中进行了靶向突变分析、既往活检回顾和临床相关性评估。所有6例TdT+ LBCL均为类胚细胞样表现，CD 34 −、MYC+、BCL 2+，并有MYC重排（R）（5/6例有BCL 2和/或BCL 6-R）。5/6例既往患有TdT− LBCL和/或滤泡性淋巴瘤，且均具有侵袭性病程。在4/5的突变病例中，11个基因中有15个非同义变异。1例TdT+和TdT−区显示相同突变。突变谱更像在生发中心B细胞型弥漫性LBCL而不是B-LBL中报道的那些。从先前的TdT-淋巴瘤的演变在1/3的测试病例中是非发散的，在2例中部分发散。这6例病例的临床病理学和细胞遗传学特征与荟萃分析中发现的特征相似，该荟萃分析包括滤泡性淋巴瘤后TdT+ LBCL或B-LBL的额外病例。因此，TdT+，CD 34-大B细胞肿瘤与MYC重排和经常是“双重打击”是罕见的，往往是一个转化事件和侵略性，但不同于经典的B-LBL。
Supplemental Digital Content is available in the text. In the current World Health Organization classification, terminal deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although TdT expression in what appear to be mature LBCL or following mature B-cell neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these cases, and their clinicopathologic features, molecular landscape, and relationship to classic B-LBL remain to be better defined. TdT expression was therefore assessed in 258 LBCL and the results correlated with the cytologic, phenotypic, and cytogenetic findings. Targeted mutational analysis, review of prior biopsies, and assessment of clinical associations was performed in the 6 cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34−, MYC+, BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a prior TdT− LBCL and/or follicular lymphoma and all had an aggressive course. Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with mutations. TdT+ and TdT− areas in 1 case showed identical mutations. The mutational profiles were more like those reported in germinal center B-cell type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT− lymphomas was nondivergent in 1/3 tested cases and partially divergent in 2. The clinicopathologic and cytogenetic features of these 6 cases were similar to those found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL following follicular lymphoma. Thus, TdT+, CD34− large B-cell neoplasms with MYC rearrangements and often a “double hit” are rare, frequently a transformational event and aggressive but are distinct from classic B-LBL.
影响因子：
8.8
作者：
Pasqualucci L;Khiabanian H;Fangazio M;Vasishtha M;Messina M;Holmes AB;Ouillette P;Trifonov V;Rossi D;Tabbò F;Ponzoni M;Chadburn A;Murty VV;Bhagat G;Gaidano G;Inghirami G;Malek SN;Rabadan R;Dalla-Favera R
通讯作者：
Dalla-Favera R
影响因子：
30.8
作者：
Zhang, Jinghui;McCastlain, Kelly;Yoshihara, Hiroki;Xu, Beisi;Chang, Yunchao;Churchman, Michelle L.;Wul, Gang;Li, Yongjin;Wei, Lei;Iacobucci, Ilaria;Liu, Yu;Qu, Chunxu;Wen, Ji;Edmonsonl, Michael;Payne-Turner, Debbie;Kaufmann, Kerstin B.;Takayanagi, Shin-ichiro;Wienholds, Erno;Waanders, Esme;Ntziachristos, Panagiotis;Bakogianni, Sofia;Wang, Jingjing;Aifantis, Iannis;Roberts, Kathryn G.;Ma, Jing;Song, Guangchun;Easton, John;Mulder, Heather L.;Chen, Xiang;Newman, Scott;Ma, Xiaotu;Rusch, Michael;Gupta, Pankaj;Boggs, Kristy;Vadodaria, Bhavin;Dalton, James;Liu, Yanling;Valentine, Marcus L.;Ding, Li;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda;Tabib, Yashodhan;Ochoa, Kerri;Devidas, Meenakshi;Pei, Deqing;Cheng, Cheng;Yang, Jun;Evans, William E.;Relling, Mary V.;Pui, Ching-Hon;Jeha, Sima;Harvey, Richard C.;Chen, I-Ming L.;Willman, Cheryl L.;Marcucci, Guido;Bloomfield, Clara D.;Kohlschmidt, Jessica;Mrozek, Krzysztof;Paietta, Elisabeth;Tallman, Martin S.;Stock, Wendy;Foster, Matthew C.;Racevskis, Janis;Rowe, Jacob M.;Luger, Selina;Kornblau, Steven M.;Shurtleff, Sheila A.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Dick, John E.;Hunger, Stephen P.;Loh, Mignon L.;Downing, James R.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.