Clinical And Genetic Analysis Of Juvenile Myelomonocytic Leukemia

Objective To analyze the clinical features and genetic of Juvenile myelomonocytic leukemia(JMML),discuss the relationship between their genotypes and prognosis,and explore a new treatment of JMML.Methods The clinical data of 14 patients diagnosed with JMML from January 2014 to January 2018 in Hunan Province were collected,and examined common gene mutations of JMML by performing PCR and second-generation sequencing methods to confirm the cases.The clinical features,genotypes,and prognosis of 14 cases were analyzed by statistical methods.Results1.Among the 14 cases,abdominal distention and fever as first symptoms which were the most common,respectively accounting for 7 cases(50.00%)and 4 cas'es(28.57%).12 out of 14 cases were male,and 2 were female.The ratio of male and female was 6:1,and males were significantly more than females.The minimum age was 2 months and the maximum was 5 years and 7 months.The median age at diagnosis was 27.5 months.There were 71.43%patients onset within 4 years of age.And the age was negatively correlated with the length of survival(r=-0.41,P=0.14).All patients had hepatosplenomegaly and superficial lymphadenopathy(100%).Blasts were easily found in the peripheral blood(PM)smears of 14 patients,and the presence of 1%to 7%blasts in the PB,as well as,the proportion of monocytes increased,which highest accounted for 40%.The bone marrow(BM)hyperplasia of 14 children with JMML was active into extremely active and blast percentage in BM<20%.2.The level of HbF was negatively correlated with the length of survival(r=-0.45,P=0.10).The level of HbF had no significant effect on the survival outcom of children with JMML,and the difference was not statistically significant(?2=0,73 Fisher's P=0.46).The level of LDH had no significant effect on the survival of children with JMML,and the difference was not statistically significant(?2=2.36 Fisher's P=0.17).3.Philadelphia chromosomes were not seen in all 14 patients,and one of which was chromosome 7 deletion.Nine cases of BCR/ABL fusion gene test were negative.4.PTPN11 gene mutations were found in 5 out of 14 cases and the mutation site was Exon3 and Exon 13.4 cases with NF1 gene mutations with or without neurofibroma type 1,and their mutation sites occurred on Exons 4,10,22,23,30.3 cases with CBL mutations,and the mutations mainly occurred on Exon8 and classical splice sites.2 cases with RAS mutations,and the mutation site occurred on exon 2.The probability of PTPN11 gene mutation was the highest,accounting for 35.71%,followed by NF1 gene mutation,CBL gene mutation and RAS gene mutation.5.Fourteen children wih JMML were followed up,of which 8 deaths and 6 survivals.The overall survival time range from 0 to 39 months,and the median survival time was 15 months.Children Cases with PTPN11 mutations had the worst prognosis and the highest fatality rate.Cases with CBL mutations had a relatively good prognosis,some of which may be spontaneously relieved or achieved hematologic improvement.Conclusions1.JMML is a rare disease with a low incidence and poor prognosis in Hunan province.2.The level of LDH and HbF have no significant effect on the survival of children with JMML.3.The type of gene mutation in children with JMML is associated with prognosis.Among which the probability of PTPN11 gene mutation is the highest in JMML,and its prognosis is the worst;patients with CBL mutations have a relatively good prognosis,some of which may be occur spontaneous resolution or achieve hematologic improvement.The therapy of DNA methyltransferase inhibitors bridging HSCT may improve the prognosis of children with JMML.