Gene mutations in the Ras pathway and the prognostic implication in Korean patients with juvenile myelomonocytic leukemia

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.