NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report
NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report
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DOI：
10.1182/blood-2014-04-570929
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发表时间：
2014-10-09
期刊：
影响因子：
20.3
通讯作者：
Meshinchi, Soheil
中科院分区：
文献类型：
--
作者：
Ostronoff, Fabiana;Othus, Megan;Meshinchi, Soheil
NUP 98/NSD 1最近被报道与急性髓性白血病（AML）的不良结局相关。先前的研究还观察到NUP 98/NSD 1和FLT 3/ITD之间的高度重叠，提出了一个问题，即报告的不良结局是由于NUP 98/NSD 1还是由这两种遗传病变的共同发生引起的。我们的目的是确定NUP 98/NSD 1在FLT 3/ITD AML背景下的预后意义。共1421例患者入组5个连续的儿童肿瘤组/儿童癌症组和SWOG试验进行了评价。NUP 98/NSD 1在15%的FLT 3/ITD和7%的细胞遗传学正常（CN）-AML中被发现。FLT 3/ITD和NUP 98/NSD 1双重患者（NUP 98/NSD 1患者的82%）的完全缓解率为27%，而FLT 3/ITD无NUP 98/NSD 1患者的完全缓解率为69%（P <0.001）。相应的3年总生存率分别为31%和48%（P = 0.011）。在CN-AML中，合并NUP 98/NSD 1和FLT 3/ITD的患者的结局比仅携带NUP 98/NSD 1的患者更差。在多变量分析中，双重NUP 98/NSD 1和FLT 3/ITD仍然是预后不良的独立预测因子，NUP 98/NSD 1不含FLT 3/ITD失去了其预后意义。我们的研究表明，NUP 98/NSD 1和FLT 3/ITD之间的相互作用决定了NUP 98/NSD 1疾病患者的不良结局。
NUP98/NSD1 has recently been reported in association with poor outcome in acute myeloid leukemia (AML). Previous studies also observed a high overlap between NUP98/NSD1 and FLT3/ITD, raising the question as to whether the reported poor outcome is due to NUP98/NSD1 or caused by the co-occurrence of these 2 genetic lesions. We aimed to determine the prognostic significance of NUP98/NSD1 in the context of FLT3/ITD AML. A total of 1421 patients enrolled in 5 consecutive Children's Oncology Group/Children's Cancer Group and SWOG trials were evaluated. NUP98/NSD1 was found in 15% of FLT3/ITD and 7% of cytogenetically normal (CN)-AML. Those with dual FLT3/ITD and NUP98/NSD1(82% of NUP 98/NSD1 patients) had a complete remission rate of 27% vs 69% in FLT3/ITD without NUP98/NSD1 (P < .001). The corresponding 3-year overall survival was 31% vs 48% (P = .011), respectively. In CN-AML, patients with concomitant NUP98/NSD1 and FLT3/ITD had a worse outcome than those harboring NUP98/NSD1 only. In multivariate analysis, the dual NUP98/NSD1 and FLT3/ITD remained an independent predictor of poor outcome, and NUP98/NSD1 without FLT3/ITD lost its prognostic significance. Our study demonstrates that it is the interaction between NUP98/NSD1 and FLT3/ITD that determines the poor outcome of patients with NUP98/NSD1 disease.