FLT3 inhibitor-induced neutrophilic dermatosis
FLT3 inhibitor-induced neutrophilic dermatosis
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DOI：
10.1182/blood-2013-01-478172
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发表时间：
2013-07-11
期刊：
影响因子：
20.3
通讯作者：
Chen, Yi-Bin
中科院分区：
文献类型：
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作者：
Fathi, Amir T.;Le, Long;Chen, Yi-Bin
FLT 3-ITD突变与急性髓系白血病预后不良相关已在临床试验中研究了多种FMS样酪氨酸激酶3（FLT 3）抑制剂。最近，有效的FLT 3抑制显示出诱导FLT 3突变型成髓细胞的终末分化。在3名患者中，他们在开始FLT 3抑制时出现特征性皮肤结节，我们对皮肤样本进行了皮肤病理学评价，以及FLT 3和NPM 1突变分析和荧光原位杂交。所有3例患者均表现出特征性的深层真皮和皮下嗜中性粒细胞浸润，无成髓细胞证据。在2个样本中发现FLT 3-ITD和NPM 1突变，以及在另一个样本中发现FLT 3-ITD和7 q缺失，证实了分化的中性粒细胞的祖先是原始FLT 3突变型成髓细胞的祖先。FLT 3抑制可导致临床上不同的皮肤病，这表明FLT 3抑制对骨髓分化的影响以及与该疗法相关的更广泛“综合征”的表现。
The FLT3-ITD mutation is associated with poor outcomes in acute myeloid leukemia. Multiple FMS-like tyrosine kinase 3 (FLT3)-inhibitors have been studied in clinical trials. Recently, potent FLT3 inhibition was shown to induce terminal differentiation of FLT3-mutant myeloblasts. In 3 patients who developed characteristic skin nodules on initiation of FLT3-inhibition, we conducted dermatopathologic evaluation of skin samples, as well as FLT3 and NPM1 mutational analysis and fluorescence in situ hybridization. All 3 patients demonstrated characteristically deep dermal and subcutaneous neutrophilic infiltrates without evidence of myeloblasts. Discovery of FLT3-ITD and NPM1 mutations in 2 of the samples, as well as the presence of FLT3-ITD and deletion of 7q in the other, confirmed the ancestry of the differentiated neutrophils as that of the original FLT3-mutant myeloblasts. FLT3 inhibition can lead to clinically distinct dermatoses, which suggests the effect of FLT3 inhibition on myeloid differentiation and a manifestation of a broader "syndrome" associated with this therapy.