期刊
LEUKEMIA
卷 29, 期 4, 页码 869-876出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2014.289
关键词
-
资金
- NIH [K08HL106576, K12HL087107, P01CA101937, T32HL007088]
- Sidney Kimmel Scholar Award
- Leukemia Research Foundation New Investigator Award
- Central Society for Clinical Research Early Career Development Award
- Barnes-Jewish Hospital Foundation/Washington University Institute of Clinical and Translational Sciences Pilot Grant
- American Cancer Society Institutional Research Grant
- Washington University Institute of Clinical and Translational Sciences Grant from the National Center for Advancing Translational Sciences of NIH [UL1TR000448]
- NCI Cancer Center Support Grant [P30CA91842]
Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single-nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据