Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes.
Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes.
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DOI：
10.1038/s41467-018-04924-z
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发表时间：
2018-07-10
影响因子：
16.6
通讯作者：
Futreal PA
中科院分区：
文献类型：
--
作者：
Takahashi K;Wang F;Morita K;Yan Y;Hu P;Zhao P;Zhar AA;Wu CJ;Gumbs C;Little L;Tippen S;Thornton R;Coyle M;Mendoza M;Thompson E;Zhang J;DiNardo CD;Jain N;Ravandi F;Cortes JE;Garcia-Manero G;Kornblau S;Andreeff M;Jabbour E;Bueso-Ramos C;Takaori-Kondo A;Konopleva M;Patel K;Kantarjian H;Futreal PA
混合表型急性白血病（MPAL）是一种罕见的急性白血病亚型，其特征是白血病原始细胞呈现髓系和淋巴样标记。在这里，我们报告了31例MPAL样本的综合基因组分析数据，并将其与急性髓性白血病（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）的分子谱进行了比较。与混合免疫表型一致，MPAL中检测到AML型和ALL型突变。髓系-B和髓系-T MPAL显示出与谱系定型基因表达差异相关的不同突变和甲基化特征。MPAL、AML、B-ALL和T-ALL之间的全基因组甲基化比较将MPAL细分为AML型和ALL型MPAL，当给予谱系匹配的治疗时，这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的遗传差异，并进一步为MPAL的分子指导精确治疗方法提供了概念证明。混合型急性白血病（MPAL）是一种罕见的白血病，在原始细胞上同时存在髓系和淋巴系标志物。在这里，作者进行了基因组分析，以显示MPAL涉及遗传和表观遗传异质性，并且在遗传上不同于AML，B-ALL和T-ALL。
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. Mixed phenotype acute leukemia (MPAL) is a rare leukemia that presents both myeloid and lymphoid markers on blasts. Here the authors perform genomic analysis to show MPAL involves genetic and epigenetic heterogeneity and is genetically distinct from AML, B-ALL, and T-ALL.
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影响因子：
28.2
作者：
Glass JL;Hassane D;Wouters BJ;Kunimoto H;Avellino R;Garrett-Bakelman FE;Guryanova OA;Bowman R;Redlich S;Intlekofer AM;Meydan C;Qin T;Fall M;Alonso A;Guzman ML;Valk PJM;Thompson CB;Levine R;Elemento O;Delwel R;Melnick A;Figueroa ME
通讯作者：
Figueroa ME
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
32.4
作者：
Johnson, Kristen;Hashimshony, Tamar;Singh, Harinder
通讯作者：
Singh, Harinder