PO.CL01.17 · 临床研究
急性髓系白血病（AML）患者的中性粒细胞性皮肤浸润为克隆性且与总生存期不良相关
Neutrophilic skin infiltrates in patients with acute myeloid leukemia (AML) are clonal and associate with poor overall survival
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤。虽然原始细胞浸润（白血病皮肤浸润，LC）是一种已知的髓外疾病，反应性中性粒细胞性皮病（如Sweet综合征）也很常见，但其病因仍不明确。我们旨在确定这些病变是否代表一种非典型的白血病过程。
方法：我们分析了1,019例连续AML患者的临床和分子特征，包括生存结局，针对经组织病理学评估的皮肤病变（诊断前10天至诊断后60天）。反应性中性粒细胞性皮病患者接受了无白血病原始细胞的确认。随后，我们对8例此类患者的骨髓（BM）和FFPE来源皮肤活检组织进行了配对肿瘤/正常全外显子组测序。
结果：31%的患者需要皮肤科会诊。虽然反应性炎症总体上显示较高的完全缓解（CR）率（91%），但反应性中性粒细胞性皮病患者在所有患者组中无病生存期（DFS）最短，中位DFS仅为13个月。临床上，这些患者常携带NPM1（27%）、IDH1/2（41%）和FLT3-ITD（23%）突变。接下来，我们对4例皮肤病变被确认为无原始细胞的患者的配对样本进行了测序。值得注意的是，皮肤病变的测序揭示了与BM原始细胞中发现的相同的AML基因突变，且两种组织中的变异等位基因分数（VAF）几乎相同。四例患者中有三例还携带编码角蛋白相关蛋白的基因突变。
结论：形态学正常但突变呈克隆性的中性粒细胞性浸润代表了白血病的一种独特髓外表现，它不同于经典的白血病皮肤浸润，但具有显著的临床和生物学意义（生存不良）。慢性粒单核细胞白血病（CMML）中已知存在类似现象。如果得到验证，这可能识别出一种未被充分认识的白血病累及类型和可能的逃逸机制。
查看英文原文 English abstract
Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. While blast infiltration (leukemia cutis, LC) is a known extramedullary disease, reactive neutrophilic dermatoses (like Sweet's syndrome) are common, but their etiology remains unclear. We aimed to determine if these lesions represent an atypical leukemic process.
Methods: We analyzed the clinical and molecular characteristics, including survival outcomes, in 1,019 consecutive AML patients for histopathologically evaluated skin lesions (10 days prior and up to 60 days post-diagnosis). Patients with reactive neutrophilic dermatoses underwent confirmation for absence of leukemic blasts. We then performed paired tumor/normal whole-exome sequencing on bone marrow (BM) and FFPE-derived skin biopsy tissues for 8 such patients.
Results: Dermatology consultation was required in 31% of patients. While reactive inflammation generally showed high complete remission (CR) rates (91%), patients with reactive neutrophilic dermatoses had the shortest disease-free survival (DFS) of all patient groups, with a median DFS of only 13 months. Clinically, these patients frequently harbored NPM1 (27%), IDH1/2 (41%), and FLT3-ITD (23%) mutations. Next, we sequenced paired samples from 4 patients whose skin lesions were confirmed as blast-free. Remarkably, sequencing of the skin lesions revealed AML gene mutations identical to those found in the BM blasts, with near-identical variant allele fractions (VAFs) in both tissues. Three of four patients also harbored mutations in genes encoding keratin-associated proteins.
Conclusions: Morphologically normal, mutationally clonal, neutrophilic infiltrates represent a distinct extramedullary manifestation of leukemia that differs from classical leukemia cutis but has significant clinical and biological relevance (poor survival). A similar phenomenon is known for chronic myelomonocytic leukemia (CMML). If validated, this may identify an underappreciated type of leukemic involvement and possible escape mechanism.
利益披露 Disclosure
G. Tesfaye, None..
Y. Abu-Shihab, None..
B. Kaffenberger, None..
A. Eisfeld, None.