Jain Preetesh, Zhang Shaojun, Kanagal-Shamanna Rashmi, Ok Chi Young, Nomie Krystle, Gonzalez Graciela Nogueras, Gonzalez-Pagan Omarya, Hill Holly A, Lee Hun Ju, Fayad Luis, Westin Jason, Nastoupil Loretta, Hagemeister Frederick, Chen Wendy, Oriabure Onyeka, Badillo Maria, Jiang Changying, Yixin Yao, Li Shaoying, Tang Guilin, Yin C Cameron, Patel Keyur P, Medeiros Leonard Jeffrey, Nair Ranjit, Ahmed Sairah, Iyer Swaminathan P, Thirumurthi Selvi, Champlin Richard, Xu Guofan, Tinsu Pan, Santos David, Wang Ruiping, Han Guangchun, Zhang Jianhua, Song Xingzhi, Neelapu Sattva, Romaguera Jorge, Futreal Andy, Flowers Christopher, Fowler Nathan, Wang Linghua, Wang Michael L
Department of Lymphoma and Myeloma.
Division of Cancer Medicine.
Blood Adv. 2020 Mar 24;4(6):1038-1050. doi: 10.1182/bloodadvances.2019001396.
Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P = .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (<50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.
母细胞样和多形性套细胞淋巴瘤（MCL）是侵袭性组织学MCL（AH-MCL）的变体。AH-MCL可原发产生（AH-DN）或由先前的经典变体MCL转化而来（AH-t）。本研究是对AH-MCL临床和基因组特征的首次综合分析。收集患者从诊断时（AH-DN）及转化时（AH-t）的特征。计算初次诊断（AH-DN）和转化后（AH-t）的生存期。进行回归树分析以评估预后变量，并对生存期进行单因素和多因素分析。对可评估的活检标本进行全外显子测序。我们确定了183例AH-MCL患者（108例为AH-DN，75例为AH-t；152例为母细胞样，31例为多形性）。中位生存期为33个月（AH-DN和AH-t分别为48个月和14个月；P = 0.001）。与生存期较差相关的因素包括年龄（≥72岁）、AH-t类别、Ki-67≥50%和体能状态差。与AH-DN相比，AH-t的非整倍体程度明显更高。转化型MCL患者表现出KMT2B突变。与低Ki-67（<50%）的AH-MCL患者相比，Ki-67≥50%的患者在CCND1、NOTCH1、TP53、SPEN、SMARCA4、RANBP2、KMT2C、NOTCH2、NOTCH3和NSD2中有独特的突变。AH-t患者预后较差且具有独特的基因组特征。这是第一项报道Ki-67高（≥50%）的AH-MCL患者表现出独特的突变特征且生存期极差的研究。
