Multiple clonal MLL fusions in a patient receiving CHOP-based chemotherapy.
Multiple clonal MLL fusions in a patient receiving CHOP-based chemotherapy.
复制标题
DOI：
10.1111/j.1365-2141.2012.09248.x
复制
发表时间：
2012-10
影响因子：
6.5
通讯作者：
Vaughan AT
中科院分区：
文献类型：
--
作者：
Shih SJ;Fass J;Buffalo V;Lin D;Singh SP;Diaz MO;Vaughan AT
使用针对外显子 12 的反向聚合酶链反应、平行测序和定制算法设计，分析了接受弥漫性大 B 细胞淋巴瘤化疗的患者血液中的 MLL 重排。在检测到的 13 个 MLL 重排中，有 5 个能够产生 MLL 融合基因，包括 MLL-MLLT3，这是急性髓系白血病 (AML) 中最常见的融合基因。其他之前在临床上未观察到的融合包括 MLL-NKD1，它是与 Wnt/β-catenin 信号传导负调节因子的融合，Wnt/β-catenin 信号传导是与白血病细胞增殖相关的途径。大多数融合体从治疗前到化疗后六个月都表现出克隆持久性，这表明融合体可能赋予突变克隆生存优势。 MLL 断点部分聚集在特定位置，表明其形成过程具有共性。此外，相同的 MLL 断点位置表现出 C 到 T 转变的 50 至 100 倍增加，与激活诱导的胞苷脱氨酶 (AICDA) 的攻击一致。正如在 AML 和急性淋巴细胞白血病中观察到的那样，在这种单一患者环境中，MLL 能够与多个融合伴侣相互作用。这一发现定义了 MLL 对碎片敏感的离散位点，与 AICDA 功能可能的失调有关。
MLL rearrangements were analysed in the blood of a patient receiving chemotherapy for diffuse large B-cell lymphoma using inverse polymerase chain reaction targeting exon 12, parallel sequencing and a custom algorithm design. Of thirteen MLL rearrangements detected, five were capable of generating MLL fusion genes, including MLL-MLLT3, the most common fusion in acute myeloid leukaemia (AML). Other fusions, all previously clinically unobserved, included MLL-NKD1, a fusion to the negative regulator of Wnt/β-catenin signaling, a pathway linked to leukaemic cell proliferation. The majority of the fusions exhibited clonal persistence from before treatment until six months post-chemotherapy, suggesting the fusions may confer a survival advantage to the mutant clone. MLL breakpoints were partly clustered at a specific location, indicating commonality in the process of their formation. Further, the same MLL breakpoint location exhibited a 50- to 100-fold increase in C to T transitions, consistent with attack by activation-induced cytidine deaminase (AICDA). As is also observed in AML and acute lymphoblastic leukaemia, in this single patient setting, MLL is capable of interacting with multiple fusion partners. This finding defines a discrete site of MLL susceptibility to fragmentation, linked to possible deregulation of AICDA function.
登录
查看更多内容
影响因子：
64.5
作者：
Robbiani DF;Bothmer A;Callen E;Reina-San-Martin B;Dorsett Y;Difilippantonio S;Bolland DJ;Chen HT;Corcoran AE;Nussenzweig A;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
9.8
作者：
Mirault, Marc-Edouard;Boucher, Patrick;Tremblay, Alain
通讯作者：
Tremblay, Alain
影响因子：
4.8
作者：
Joo, Heui-Yun;Jones, Amada;Wang, Hengbin
通讯作者：
Wang, Hengbin
影响因子：
--
作者：
Reddy, KS;Parsons, L;Chan, JA
通讯作者：
Chan, JA
影响因子：
4.8
作者：
Chapman, ER;An, S;Jahn, R
通讯作者：
Jahn, R