FLT3-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification.
FLT3-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification.
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DOI：
10.3390/biology10030243
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发表时间：
2021-03-21
期刊：
影响因子：
4.2
通讯作者：
Emadi A
中科院分区：
文献类型：
--
作者：
Li AY;Kashanian SM;Hambley BC;Zacholski K;Duong VH;El Chaer F;Holtzman NG;Gojo I;Webster JA;Norsworthy KJ;Smith BD;DeZern AE;Levis MJ;Baer MR;Kamangar F;Ghiaur G;Emadi A
约12-38%的急性早幼粒细胞白血病（APL）患者携带FLT 3-ITD突变，该突变与几种不良预后指标相关，如高白色血细胞计数、M3 v变异形态和bcr 3亚型。我们旨在回顾性研究FLT 3-ITD突变对APL患者临床特征、治疗过程和结局的影响。我们证明Sanz高危状态APL与高FLT 3-ITD等位基因负荷相关，等位基因负荷每增加1%与白色血细胞计数（WBC）增加0.6 × 109/L相关。FLT 3-ITD的存在与缓解率降低和诊断后5年死亡率升高相关。这些发现提供了新的启示FLT 3-ITD APL的功能，特别是在等位基因负担，值得进一步研究。FLT 3-ITD在急性早幼粒细胞白血病（APL）中的意义尚未明确。我们对138例APL患者进行了一项双中心回顾性研究，其中59例（42.8%）患有FLT 3-ITD。伴有FLT 3-ITD的APL患者的基线白色血细胞计数（WBC）较高（p < 0.001），较高的血红蛋白，（p = 0.03），天冬氨酸转氨酶升高（p = 0.001），血小板减少（p = 0.004），纤维蛋白原降低（p = 0.003），以及更高的弥散性血管内凝血（p = 0.005）、M3 v变异形态（p < 0.001）和bcr 3亚型（p < 0.001）的发生率。FLT 3-ITD与较差的巩固后完全缓解（CR）（p = 0.02）和79.7%的5年总生存率（OS）相关，而FLT 3-WT（野生型）为94.4%（p = 0.02）。FLT 3-ITD与基线WBC ≥ 25 × 109/L密切相关（比值比（OR）：54.4; 95% CI：10.4-286.1; p < 0.001）。高FLT 3-ITD等位基因负荷与高风险（HR）Sanz评分和高WBC相关，等位基因负荷每增加1%，对应WBC增加0.6 × 109/L。与低危（LR）APL相比，HR APL与等位基因负荷增加38.5%相关（95% CI：19.8-57.2; p < 0.001）。我们的研究结果提供了额外的证据，FLT 3-ITD APL是APL的一个独特的亚型，值得进一步研究，以描绘治疗方法的潜在差异。
Around 12–38% of acute promyelocytic leukemia (APL) patients carry the FLT3-ITD mutation, which has been associated with several poor-prognosis indicators such as high white blood cell counts, M3v variant morphology, and the bcr3 isoform. We aimed to retrospectively study the impact of FLT3-ITD mutations in APL patients in regard to clinical features, treatment courses, and outcomes. We demonstrate that Sanz high-risk status APL correlates with high FLT3-ITD allelic burdens, with every 1% increase in allelic burden correlating with a 0.6 × 109/L increase in white blood cell count (WBC). The presence of FLT3-ITD was associated with decreased remission rates and higher 5-year mortality from the time of diagnosis. These findings provide novel revelations regarding the features of FLT3-ITD APL, particularly in regard to allelic burden, that warrant further study. The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p < 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p < 0.001), and the bcr3 isoform (p < 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p < 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p < 0.001). Our results provide additional evidence that FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.
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影响因子：
6.2
作者：
Gill, Harinder S.;Yim, Rita;Kwong, Yok-Lam
通讯作者：
Kwong, Yok-Lam
影响因子：
11.4
作者：
Callens, C;Chevret, S;Dombret, H
通讯作者：
Dombret, H
全反式视黄酸/三氧化二砷治疗新诊断的急性早幼粒细胞白血病的长期疗效和安全性。
DOI：
10.1073/pnas.0813280106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Hu, Jiong;Liu, Yuan-Fang;Chen, Zhu
通讯作者：
Chen, Zhu
DOI：
10.3324/haematol.2009.015073
发表时间：
2010-05-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
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作者：
Carmen Chillon, Maria;Santamaria, Carlos;Gonzalez, Marcos
通讯作者：
Gonzalez, Marcos
表观遗传修饰基因突变是全反式视黄酸和三氧化二砷治疗急性早幼粒细胞白血病的不良预后因素。
影响因子：
11.1
作者：
Shen Y;Fu YK;Zhu YM;Lou YJ;Gu ZH;Shi JY;Chen B;Chen C;Zhu HH;Hu J;Zhao WL;Mi JQ;Chen L;Zhu HM;Shen ZX;Jin J;Wang ZY;Li JM;Chen Z;Chen SJ
通讯作者：
Chen SJ