Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, South Korea.
Ann Hematol. 2012 Apr;91(4):511-7. doi: 10.1007/s00277-011-1326-9. Epub 2011 Sep 8.
Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Hyperactivation of the Ras pathway from gene mutations is known to be the key culprit in the development of JMML. In this study, we investigated Ras pathway mutations and prognostic implication in Korean patients with JMML. A total of 22 Korean patients with JMML were recruited from two institutions (19 boys and three girls; median age, 17 months; range, 1-74 months). Hematologic and cytogenetic findings were reviewed. Mutation analyses involved PTPN11, KRAS, NRAS, and CBL genes by direct sequencing analyses (selected exons except in CBL). Survival analysis was performed by the Kaplan-Meier method. Cytogenetic and/or gene mutations were detected in 18 patients out of 22 (82%). Four patients (18%) had chromosomal abnormalities, with monosomy 7 being the most common. Seventeen (77%) had gene mutations. PTPN11 mutations were detected in 13 patients (59%). The patient heterozygous for c.854T>C had Noonan syndrome. NRAS and KRAS mutations were detected in two patients (9%) and one patient (5%), respectively. A homozygous CBL mutation was detected in one patient (5%; c.1228-2A>G). All mutations detected were previously reported mutations. Survival analyses suggested an unfavorable prognostic implication of PTPN11 mutation, albeit without a statistical significance. Collectively, the results from molecular genetics study and survival analyses suggested a relatively higher frequency and unfavorable prognostic implication of PTPN11 mutations in Korean patients with JMML.
儿童幼年髓单核细胞白血病（JMML）是一种罕见的血液系统恶性肿瘤。已知基因突变导致 Ras 通路的过度激活是 JMML 发展的关键罪魁祸首。在这项研究中，我们调查了 Ras 通路突变与韩国 JMML 患者的预后相关性。共从两个机构招募了 22 名韩国 JMML 患者（19 名男孩和 3 名女孩；中位年龄 17 个月；范围 1-74 个月）。回顾了血液学和细胞遗传学发现。通过直接测序分析（除 CBL 外，选择外显子）检测 PTPN11、KRAS、NRAS 和 CBL 基因的突变分析。通过 Kaplan-Meier 方法进行生存分析。在 22 名患者中有 18 名（82%）检测到细胞遗传学和/或基因突变。4 名患者（18%）存在染色体异常，最常见的是单体 7。17 名（77%）患者有基因突变。在 13 名患者（59%）中检测到 PTPN11 突变。杂合 c.854T>C 的患者患有 Noonan 综合征。在 2 名患者（9%）和 1 名患者（5%）中分别检测到 NRAS 和 KRAS 突变。在 1 名患者（5%；c.1228-2A>G）中检测到纯合 CBL 突变。所有检测到的突变均为先前报道的突变。生存分析表明 PTPN11 突变具有不良的预后意义，尽管无统计学意义。总之，分子遗传学研究和生存分析的结果表明，PTPN11 突变在韩国 JMML 患者中相对更为常见且具有不良预后意义。
