Supplementary Material for: Adult Acute Myeloid Leukemia with the KMT2A-Mixed Lineage Leukemia T10 Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway

Mixed lineage leukemia (MLL) T10 is a relatively rare partner for the KMT2A lysine (K)-specific methyltransferase 2A gene. The common features and coexisting mutations of acute myeloid leukemia (AML) patients with KMT2A-MLLT10 remain unknown. In this study, 10 adult AML patients with KMT2A-MLLT10 fusions were picked up from 496 AML patients by using RT-polymerase chain reaction (PCR) and/or fluorescence in situ hybridization, and then screened for mutations in the 49 genes panel with next-generation sequencing and PCR, followed by direct Sanger sequencing. Of the 10 unique individuals identified, 6 were male and 4 were female (M:F ratio, 1.5:1) with ages ranging from 19 to 52 years (median 39.5 years). Most (90%, 9/10) patients with KMT2A-MLLT10 were accompanied by additional mutations. Twelve mutated genes were detected, averaging 2.1 mutations per patient (range, 0–4). The most frequently mutated gene was NRAS (n = 5). Clinical and laboratory data pointed to common features: French American British-M5 subtype (n = 7), a high rate of relapse, and biomarkers CD33 (n = 10), CD117 (n = 9), CD13 (n = 8), and CD64 (n = 8). Overall, most patients harbored at least one mutation. A high incidence of mutations affecting the RAS signaling pathway or RAS regulating components was found in 50% (5/10) patients. The overall survival is about 12.0 months. Allogeneic-hematopoietic stem cell transplantation trends to improve survival in selected patients.

混合谱系白血病（MLL）T10是赖氨酸特异性甲基转移酶2A（KMT2A）基因较为罕见的融合伴侣基因。目前，携带KMT2A-MLLT10融合基因的急性髓系白血病（AML）患者的临床特征及共存突变情况仍不明确。本研究从496例急性髓系白血病患者中，通过逆转录聚合酶链反应（RT-PCR）和/或荧光原位杂交（FISH）技术筛选出10例携带KMT2A-MLLT10融合基因的成人AML患者；随后采用下一代测序技术及聚合酶链反应对49基因组合进行突变筛查，并通过直接桑格测序（Sanger sequencing）进行验证。在本研究筛选出的10例独立患者中，男性6例、女性4例，男女比例为1.5:1，年龄区间为19~52岁，中位年龄39.5岁。90%（9/10）的KMT2A-MLLT10融合阳性患者伴随其他共存突变。本研究共检测到12个突变基因，每位患者平均携带2.1个突变（范围0~4个），其中突变频率最高的基因为NRAS（n=5）。临床及实验室数据显示该类患者具有以下共同特征：法美英（FAB）分型M5亚型共7例、高复发率，免疫表型标志物CD33（10例）、CD117（9例）、CD13（8例）及CD64（8例）阳性。总体而言，多数患者至少携带1个突变。50%（5/10）的患者存在影响RAS信号通路或RAS调控组分的突变，突变发生率较高。患者总生存期约为12.0个月。异基因造血干细胞移植或可改善符合指征患者的生存预后。