Objective: To study the clinical and genetic features of juvenile myelomonocytic leukemia (JMML) and the association between genotype and prognosis. Methods The clinical data of 15 children who were diagnosed with JMML were collected. Next-generation sequencing was used to detect common gene mutations of JMML.
Results: The male/female ratio was 6.5:1, and the age of onset was 19 months (range 2-67 months). Of the 15 children, 11 (73%) experienced disease onset before the age of 4 years, with abdominal distension and pyrexia as initial symptoms. All children had hepatosplenomegaly and superficial lymphadenectasis, with a number of peripheral blood mononuclear cells of >1.0×109/L and a percentage of juvenile cells of 1%-7% in peripheral blood smear. The percentage of bone marrow blasts + juvenile cells was <20%, and the percentage of monoblasts + promonocytes was 1%-10%. Of the 15 children, 10 (67%) had a higher level of hemoglobin F than the normal level at the corresponding age, with the highest level of 62.5%. All 15 children had the absence of Philadelphia chromosome, and one child had chromosome 7 deletion. All 15 children had a negative result of BCR/ABL fusion gene detection. PTPN11 gene mutation was found in 5 children (33%), NF1 mutation in 4 children (27%), CBL mutation in 3 children (20%), and RAS mutation in 3 children (20%). No children received regular chemotherapy, and one child underwent hematopoietic stem cell transplantation. The median follow-up time of 15 children was 18 months (range 1-48 months). Among the 15 children, 8 died (among whom 4 had PTPN11 gene mutation, 3 had NF1 mutation, and 1 had RAS mutation) and 7 survived. The children with PTPN11 mutation had the worst prognosis and the highest mortality rate, and those with CBL or NRAS mutation had a relatively good prognosis. The level of hemoglobin F was negatively correlated with survival time (rs=-7.21, P=0.002).
Conclusions: In children with JMML, the type of gene mutation is associated with prognosis. The children with PTPN11 mutation often have a poor prognosis, and those with CBL or NRAS mutation have a relatively good prognosis.
目的: 对幼年型粒单核细胞白血病（JMML）患儿进行临床及基因学特点分析，探讨基因型与预后的关系。
方法: 收集15例临床诊断JMML患儿的临床资料，采用二代测序方法进行JMML常见突变基因检测。
结果: 15例JMML患儿中男女比例为6.5：1，发病年龄为19（2~67）月，11例（73%）患儿为4岁以内发病，首发症状以腹胀、发热多见，所有患儿均有肝脾及浅表淋巴结肿大，外周血单核细胞均> 1.0×109/L、外周血涂片幼稚细胞比例1%~7%、骨髓原始细胞+幼稚细胞均 < 20%、骨髓原始单核+幼稚单核细胞1%~10%。10例（67%）患儿的血红蛋白F（HbF）高于相应年龄正常值，最高62.5%。15例患儿均未见Ph染色体，其中1例存在7号染色体缺失。15例患儿BCR/ABL融合基因均阴性，5例（33%）检测到PTPN11基因突变，4例（27%）NF1基因突变，3例（20%）CBL基因突变，3例（20%）RAS基因突变。除1例行造血干细胞移植外，其余均未予规律化疗。15例JMML患儿的随访时间为18（1~48）个月，死亡8例（其中4例为PTPN11基因突变患儿，3例为NF1基因突变患儿，1例为RAS基因突变患儿），存活7例。存在PTPN11基因突变的患儿预后最差，病死率最高。CBL及NRAS基因突变的患儿预后相对较好。HbF水平与生存期呈负相关（rs=-7.21，P=0.002）。
结论: JMML患儿基因突变类型与预后相关，存在PTPN11基因突变的预后最差，具有CBL及NRAS基因突变的患儿预后较好。