Durable Disease Control with MEK Inhibition in a Patient with NRAS-mutated Atypical Chronic Myeloid Leukemia
Durable Disease Control with MEK Inhibition in a Patient with NRAS-mutated Atypical Chronic Myeloid Leukemia
复制标题
DOI：
10.7759/cureus.414
复制
发表时间：
2015-12-01
影响因子：
1.2
通讯作者：
Druker, Brian J.
中科院分区：
文献类型：
--
作者：
Khanna, Vishesh;Pierce, Scott T.;Druker, Brian J.
非典型慢性粒细胞白血病（aCML）和慢性嗜中性粒细胞白血病（CNL）是罕见的血液肿瘤，其特征是白细胞增多和骨髓细胞增多。尽管在（CNL）患者中经常观察到集落刺激因子3受体（CSF 3R）的复发性突变，但（aCML）的突变情况不太明确。在这份报告中，我们描述了一个81岁的男性谁被诊断为慢性粒细胞白血病。他表现为白细胞增多和贫血，但没有明显的临床症状。标准的实验室研究表明，费城染色体的缺失。大规模平行测序表明CSF 3R中没有突变，但存在杂合NRAS-G12 D变体（47%等位基因频率）。患者开始接受曲美替尼治疗，曲美替尼是一种MEK 1/2抑制剂，已获得食品和药物管理局批准用于恶性黑色素瘤。曲美替尼治疗导致他的血细胞计数异常改善，并在14个月的随访中继续控制疾病。该病例强调需要进行临床试验，以评估MEK 1/2作为治疗NRAS突变的aCML/CNL患者的治疗靶点的安全性和有效性。
Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare hematologic neoplasms characterized by leukocytosis and a hypercellular bone marrow. Although recurrent mutations in the colony-stimulating factor 3 receptor (CSF3R) are frequently observed in patients with (CNL), the mutational landscape in (aCML) is less welldefined. In this report, we describe an 81-year-old male who was diagnosed with aCML. He presented with leukocytosis and anemia but no significant clinical symptoms. Standard laboratory studies revealed the absence of the Philadelphia chromosome. Massively parallel sequencing demonstrated no mutations in CSF3R, but the presence of a heterozygous NRAS-G12D variant (47% allele frequency). The patient was started on treatment with trametinib, an MEK1/2 inhibitor with Food and Drug Administration approval for malignant melanoma. Therapy with trametinib resulted in exceptional improvements in his blood counts and continued disease control with 14 months of follow-up. This case highlights the need for clinical trials evaluating the safety and efficacy of MEK1/2 as a therapeutic target for the treatment of patients with NRAS-mutated aCML/CNL.