Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2018 Jul 10;9(1):2670. doi: 10.1038/s41467-018-04924-z.
Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by leukemic blasts presenting myeloid and lymphoid markers. Here we report data from integrated genomic analysis on 31 MPAL samples and compare molecular profiling with that from acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B-ALL), and T cell acute lymphoblastic leukemia (T-ALL). Consistent with the mixed immunophenotype, both AML-type and ALL-type mutations are detected in MPAL. Myeloid-B and myeloid-T MPAL show distinct mutation and methylation signatures that are associated with differences in lineage-commitment gene expressions. Genome-wide methylation comparison among MPAL, AML, B-ALL, and T-ALL sub-classifies MPAL into AML-type and ALL-type MPAL, which is associated with better clinical response when lineage-matched therapy is given. These results elucidate the genetic and epigenetic heterogeneity of MPAL and its genetic distinction from AML, B-ALL, and T-ALL and further provide proof of concept for a molecularly guided precision therapy approach in MPAL.
混合表型急性白血病（MPAL）是一种罕见的急性白血病亚型，其特征是白血病母细胞呈现髓系和淋系标志物。在此，我们报告了 31 例 MPAL 样本的综合基因组分析数据，并将分子谱与急性髓系白血病（AML）、B 细胞急性淋巴细胞白血病（B-ALL）和 T 细胞急性淋巴细胞白血病（T-ALL）进行了比较。与混合免疫表型一致，MPAL 中同时检测到 AML 型和 ALL 型突变。髓系-B 和髓系-T MPAL 显示出不同的突变和甲基化特征，与谱系定向基因表达的差异相关。在 MPAL、AML、B-ALL 和 T-ALL 亚类之间进行的全基因组甲基化比较将 MPAL 分为 AML 型和 ALL 型 MPAL，当给予与谱系匹配的治疗时，与更好的临床反应相关。这些结果阐明了 MPAL 的遗传和表观遗传异质性及其与 AML、B-ALL 和 T-ALL 的遗传区别，并进一步为 MPAL 中基于分子指导的精准治疗方法提供了概念验证。
