Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.
Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.
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DOI：
10.1016/j.ccr.2011.09.011
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发表时间：
2011-11-15
期刊：
影响因子：
50.3
通讯作者：
Bhatia R
中科院分区：
文献类型：
--
作者：
Li L;Li M;Sun C;Francisco L;Chakraborty S;Sabado M;McDonald T;Gyorffy J;Chang K;Wang S;Fan W;Li J;Zhao LP;Radich J;Forman S;Bhatia S;Bhatia R
治疗相关性骨髓增生或急性髓系白血病（t-MDS/AML）是癌症治疗的主要并发症。我们比较了自体造血细胞移植（aHCT）治疗淋巴瘤后发生t-MDS/AML的患者与未发生t-MDS/AML的对照组CD34+细胞的基因表达。我们在随后发展为t-MDS/AML的患者的ahct前样本中观察到与线粒体功能、代谢和造血调节相关的基因表达改变。向显性t-MDS/AML的进展与细胞周期调节基因的额外改变有关。一个最佳的38个基因PBSC分类器准确地区分了独立患者组中发生或未发生t-MDS/AML的患者。我们的结论是，与t-MDS/AML相关的遗传程序在疾病发病之前就被扰乱了，并准确地识别出有这种并发症风险的患者。
Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a major complication of cancer treatment. We compared gene expression in CD34+ cells from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for lymphoma with controls who did not develop t-MDS/AML. We observed altered gene expression related to mitochondrial function, metabolism, and hematopoietic regulation in pre-aHCT samples from patients who subsequently developed t-MDS/AML. Progression to overt t-MDS/AML was associated with additional alterations in cell-cycle regulatory genes. An optimal 38-gene PBSC classifier accurately distinguished patients who did or did not develop t-MDS/AML in an independent group of patients. We conclude that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and accurately identify patients at risk for this complication.
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