Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC rearrangement.
Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC rearrangement.
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DOI：
10.3324/haematol.2021.280557
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发表时间：
2023-03-01
期刊：
影响因子：
10.1
通讯作者：
Russell, Lisa J.
中科院分区：
文献类型：
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作者：
Bomken, Simon;Enshaei, Amir;Schwalbe, Edward C.;Mikulasova, Aneta;Dai, Yunfeng;Zaka, Masood;Fung, Kent T. M.;Bashton, Matthew;Lim, Huezin;Jones, Lisa;Karataraki, Nefeli;Winterman, Emily;Ashby, Cody;Attarbaschi, Andishe;Bertrand, Yves;Bradtke, Jutta;Buldini, Barbara;Burke, G. A. Amos;Cazzaniga, Giovanni;Goehring, Gudrun;de Groot-Kruseman, Hesta A.;Haferlach, Claudia;Lo Nigro, Luca;Parihar, Mayur;Plesa, Adriana;Seaford, Emma;Sonneveld, Edwin;Strehl, Sabine;van der Velden, Vincent H. J.;Rand, Vikki;Hunger, Stephen P.;Harrison, Christine J.;Bacon, Chris M.;van Delft, Frederik W.;Loh, Mignon L.;Moppett, John;Vormoor, Josef;Walker, Brian A.;Moorman, Anthony V.;Russell, Lisa J.
罕见情况下，免疫表型不成熟的 B 细胞前体急性淋巴细胞白血病 (BCP-ALL) 携带免疫球蛋白-MYC 重排 (IG-MYC-r)。这可能导致与伯基特淋巴瘤/白血病的诊断混淆以及使用未经证实疗效的个体化治疗方案。在这里，我们比较这些病症的分子特征并研究历史临床结果数据。我们确定了在国家 BCP-ALL 临床试验/注册中注册的 90 例病例。当存在时，诊断材料进行细胞遗传学、外显子组、甲基化组和转录组分析。分析的结果是 3 年无事件生存率和总生存率。 IG-MYC-r 在不同的细胞遗传学背景中被鉴定，与既定的 BCP-ALL 特异性异常共存（高超二倍体，n=3；KMT2A 重排，n=6；iAMP21，n=1；BCR-ABL1，n=1）； BCL2/BCL6-重排（n=15）；或者，最常见的是，作为唯一的定义特征 (n=64)。在最后一组中，前体样 V(D)J 断点占主导地位 (8/9)，KRAS 突变很常见 (5/11)。 DNA 甲基化鉴定出一组 V(D)J 重排病例，与伯基特白血病/淋巴瘤明显不同。该亚组中患有 IG-MYC-r 的儿童的 3 年无事件生存率为 47%，总生存率为 60%，代表高风险 BCP-ALL。为了制定有效的管理策略，必须允许这组患者获得当代的、适应微小残留病的前瞻性临床试验方案。
Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either established BCP-ALL-specific abnormalities (high hyperdiploidy, n=3; KMT2A-rearrangement, n=6; iAMP21, n=1; BCR-ABL1, n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J-rearranged cases, clearly distinct from Burkitt leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.
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影响因子：
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