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T. Kaburagi et al.
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Figure 3. Prognostic significance of NF1, PTPN11, and NRAS alterations in pediatric patients with acute myeloid leukemia. (A), (C), and (E) show Kaplan–Meier curves of overall survival of patients with and without NF1, PTPN11, and NRAS alterations. (B), (D), and (F) show Kaplan–Meier curves of event-free survival of patients with and without NF1, PTPN11, and NRAS alterations.
We also detected 15 PTPN11 mutations including two novel mutations (Table 2). In several previous studies, PTPN11 mutations have been reported to be associated with acute monoblastic leukemia (FAB-M5),4,7 however, no such tendency was observed in this study (data was not shown). PTPN11 mutations in our cohort were frequently detected in AML, minimally differentiated (FAB-M0) (P=0.026) and erythroleukemia (FAB-M6) (P=0.047). Goemans et al. also reported that the prevalence of PTPN11 was not increased in acute monoblastic leukemia (FAB-M5) suggesting that differences could exist in the ethnic back- ground of the patients studied.45 In a study by Alfayez et al., PTPN11 mutation in adult AML patients was associated with adverse prognosis.4 However, the prognostic relevance of PTPN11 has not been reported in pediatric AML.6,7 In this study, patients with PTPN11 mutations had a high frequen-
cy of RUNX1 mutations, MECOM high expression, and PRDM16 high expression which are strongly associated with poor prognosis (Figure 1; Online Supplementary Table S4).30,33,46-48 In our study, PTPN11 mutations were associated with poor EFS in univariate analysis; however, multivariate analysis revealed no significant impact of PTPN11 muta- tions on EFS or OS (Figure 3; Table 3). A significantly greater proportion of patients with PTPN11 mutations received SCT (Online Supplementary Table S4); in addition, five of 11 patients with events were rescued by SCT (Figure 1). We consider that AML patients with PTPN11 mutations tended to have a high frequency of relapse or induction failure, and some of these patients were successfully rescued by SCT.
Consistent with a previous report,49 NRAS mutations were significantly more frequently detected in CBFB- MYH11 (Figure 1; Online Supplementary Table S4). Previous
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