A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication
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DOI:
10.1038/sj.leu.2403458
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发表时间:
2004-10-01
期刊:
影响因子:
11.4
通讯作者:
Wood, BL
Wood, BL
中科院分区:
医学1区
文献类型:
--
作者:
Kussick, SJ;Stirewalt, DL;Wood, BL

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在华盛顿大学血液病理学实验室对非早幼粒细胞/非单核细胞急性髓系白血病(AML)进行的为期5年的调查中,我们发现了19例在10%或更多的原始细胞中含有独特的杯状核凹陷(AML-Cuplike)。其中14例(74%)表现为近完全缺失,其余5例表现为部分缺失。共有16例(84%)发现了Flt3基因的内部串联重复(ITD)。与缺乏这种核形态的一组选定的AML相比,AML杯状细胞明显更有可能缺乏HLA-DR和CD34的表达,表达CD123而不表达CD133,具有正常的核型,并含有Flt3ITD。为了描述一系列未选择的急性髓系白血病的AML杯状特征,我们分析了2002年6个月期间在我们实验室诊断的42例连续的非早幼粒细胞/非单核细胞急性髓系白血病。值得注意的是,在这个未经选择的系列中,如果这三个特征不相关,在核形态内陷、HLA-DR丢失和Flt3ITD存在方面存在统计学上显著的一致性,这表明具有这三个特征的AML可能代表着一个不同的AML亚集。
In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AML-cuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AML-cuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.