Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2015 Jul;90(7):653-6. doi: 10.1002/ajh.24031.
Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R-mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1-mutated and ASXL1-unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1-mutated and SETBP1-unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1-184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8-298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R-mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively.
集落刺激因子 3 受体基因 (CSF3R) 突变最近与慢性中性粒细胞白血病 (CNL) 相关。对 14 名 CSF3R 突变的 CNL 患者（中位年龄 67 岁；男性占 57%）进行了额外突变的筛查；分别有 8 名（57%）和 5 名（38%）患者携带 ASXL1 和/或 SETBP1 突变（两名患者同时表达两种突变）。两名患者发生了原始细胞转化，均为 SETBP1 突变且 ASXL1 未突变，而另外两例则进展为慢性粒单核细胞白血病（CMML），均为 ASXL1 突变且 SETBP1 未突变。中位生存时间为 23.2 个月（有 10 例死亡记录）。多变量分析显示，突变型 ASXL1（P = 0.009；HR 19.6，95%CI 2.1-184.1）和血小板减少症（P = 0.005；HR 28.8，95%CI 2.8-298.2）是独立的生存预后不良因素。本研究提供了 CSF3R 突变型 CNL 的自然史信息，并确定了突变型 ASXL1 和血小板减少症是生存的危险因素。该研究还表明 SETBP1 和 ASXL1 突变分别在疾病向原始细胞转化疾病和 CMML 进展中起致病作用。
