Retrospective nationwide survey of pediatric RDD in Japan: a high prevalence of mutations in the kinase pathway genes.

IF 1.7 4区医学 Q3 HEMATOLOGY

International Journal of Hematology Pub Date : 2025-03-10 DOI:10.1007/s12185-025-03962-w

Takeshi Asano, Akira Morimoto, Atsuko Nakazawa, Takahiro Ueda, Chitose Ogawa, Naoki Sakata, Keisuke Sugimoto, Jotaro On, Yoshiyuki Takahashi, Naoki Otsuki, Yuichi Taneyama, Nobuyuki Hyakuna, Takashi Ishihara, Akihiko Matsumine, Yoko Shioda, Kenichi Sakamoto, Yozo Nakazawa, Takahiro Yasumi, Takehiko Doi, Yuhki Koga

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引用次数: 0

Abstract

Background: Rosai-Dorfman-Destombes disease (RDD) is a rare form of histiocytosis, characterized by the accumulation of S100 protein-positive and CD1a-negative histiocytes with emperipolesis. Recently, oncogenic mutations in mitogen-activated protein kinase pathway genes were reported in nearly half of RDD patients.

Methods: We conducted a nationwide retrospective survey of childhood RDD in Japan.

Results: We found nine patients (five boys and four girls) with a median age at diagnosis of 8 years and 3 months (range, 9 months to 15 years 5 months). Two patients had nodal lesions only, three had extra-nodal lesions only, and four had both. PD-L1 was expressed in all cases. Two were resolved without treatment. Three were treated with prednisolone, one with surgery and radiation, and three with chemotherapy. Two were complicated by glomerulonephritis. Somatic pathogenic mutations in the kinase pathway genes were found in five of the six patients analyzed (three in MAP2K1, one in KRAS, and one in TSC1). Two chemotherapy-resistant patients with MAP2K1 mutations responded to trametinib. Within a median follow-up of 4 years and 9 months, two died of disease.

Conclusion: Most children with RDD carry mutations in the kinase pathway genes. Mutation analysis is suggested for patients with refractory disease.

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日本儿童RDD的回顾性全国调查：激酶通路基因突变的高流行率。

背景：Rosai-Dorfman-Destombes病（RDD）是一种罕见的组织细胞增多症，其特征是S100蛋白阳性和cd1a阴性的组织细胞聚集，并伴有外周血增多。最近，在近一半的RDD患者中报道了丝裂原活化蛋白激酶途径基因的致癌突变。方法：我们对日本儿童RDD进行了全国性的回顾性调查。结果：我们发现9例患者（5男4女），诊断时的中位年龄为8岁零3个月（范围从9个月到15岁5个月）。2例患者仅有淋巴结病变，3例仅有淋巴结外病变，4例两者均有。所有病例均表达PD-L1。其中2例未经治疗而痊愈。其中3人接受强的松龙治疗，1人接受手术和放疗，3人接受化疗。2例合并肾小球肾炎。在分析的6例患者中，有5例发现了激酶通路基因的体细胞致病性突变（3例在MAP2K1中，1例在KRAS中，1例在TSC1中）。两名MAP2K1突变的化疗耐药患者对曲美替尼有反应。在平均4年零9个月的随访期间，有两人死于疾病。结论：大多数RDD患儿携带激酶通路基因突变。建议对难治性疾病患者进行突变分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Hematology 医学-血液学

CiteScore

3.90

自引率

4.80%

发文量

223

审稿时长

6 months

期刊介绍： The International Journal of Hematology, the official journal of the Japanese Society of Hematology, has a long history of publishing leading research in hematology. The journal comprises articles that contribute to progress in research not only in basic hematology but also in clinical hematology, aiming to cover all aspects of this field, namely, erythrocytes, leukocytes and hematopoiesis, hemostasis, thrombosis and vascular biology, hematological malignancies, transplantation, and cell therapy. The expanded [Progress in Hematology] section integrates such relevant fields as the cell biology of stem cells and cancer cells, and clinical research in inflammation, cancer, and thrombosis. Reports on results of clinical trials are also included, thus contributing to the aim of fostering communication among researchers in the growing field of modern hematology. The journal provides the best of up-to-date information on modern hematology, presenting readers with high-impact, original work focusing on pivotal issues.