Cuplike Nuclei (Prominent Nuclear Invaginations) in Acute Myeloid Leukemia Are Highly Associated With FLT3 Internal Tandem Duplication and NPM1 Mutation
Cuplike Nuclei (Prominent Nuclear Invaginations) in Acute Myeloid Leukemia Are Highly Associated With FLT3 Internal Tandem Duplication and NPM1 Mutation
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DOI：
10.1002/cncr.24610
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发表时间：
2009-12-01
期刊：
影响因子：
6.2
通讯作者：
Bueso-Ramos, Carlos E.
中科院分区：
文献类型：
--
作者：
Chen, Weina;Konoplev, Sergej;Bueso-Ramos, Carlos E.
背景：一小部分急性髓系白血病 (AML) 患者具有杯状细胞核。其他研究人员已经证明这些肿瘤具有独特的临床病理学和分子特征。方法：作者在他们的机构中寻找了 10 年以上患有杯状核 AML 的患者。使用了杯状核的严格定义：>= 10% 的原始细胞，核内陷位于 >= 25% 的核区域。回顾了相关数据，并将结果与无杯样核 AML 患者的对照组进行了比较。结果：总共有 22 名杯状核 AML 患者被鉴定，并被分类为未成熟 AML（法国-美国-英国分类 M1）。与对照组（AML M1）相比，杯状核 AML 患者与 fms 样酪氨酸激酶 3 (FLT3)-内部串联重复 (ITD) 显着相关（分别为 86% 和 38%；P = .002);核磷蛋白 1 (NPM1) 突变（86% vs 19%；P < .0001）两种突变（77% vs 14%；P < .0001）；正常核型（86% vs 40%；P = .003）；骨髓原始细胞计数（90% vs 84%；P = 016）；髓过氧化物酶阳性（95% vs 30% 原始细胞；P = .001）； D-二聚体水平较高（>5000 ng/mL vs 569 ng/mL；P = .001）；且不存在 CD7（91% vs 52%；P = .007）、CD34（82% vs 5% P < .0001）和 D 相关人类白细胞抗原（59% vs 10%；P = .001）。年龄性别或外周血计数没有差异。 FLT3-ITD、NPM1 和两种突变识别杯状核 AML 的阳性预测值分别为 81%、86% 和 77%。结论：杯状核和 AML 与 NPM1 和 FLT3-ITD 突变的存在以及多种临床病理学和免疫表型特征高度相关。识别具有杯状核的 AML 的独特形态学特征可能有助于对这些肿瘤进行检查。癌症 2009，115：5481-9 (C) 2009 美国癌症协会。
BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: >= 10% blasts with nuclear invaginations in >= 25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cup like nuclei were identified and were classified as AML without maturation (French-American-British classification M1) Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86% vs 38%, respectively; P = .002 ); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001) both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P = .003); bone marrow blast count (90% vs 84%; P = 016); myeloperoxidase positivity (95% vs 30% blasts; P = .001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P = .001); and the absence of CD7 (91% vs 52%; P = .007), CD34 (82% vs 5% P < .0001) and human leukocyte antigen, D-related (59% vs 10%; P = .001). There were no differences in age sex or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS: Cuplike nuclei an AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in steaming the workup of these neoplasms. Cancer 2009, 115:5481-9 (C) 2009 American Cancer Society.