PTPN11 mutation with additional somatic alteration indicates unfavorable outcome in juvenile myelomonocytic leukemia: a retrospective clinical study from a single center

Abstract

Juvenile myelomonocytic leukemia (JMML) is a heterogeneous childhood leukemia. The management of patients with JMML requires accurate assessment of genetic and clinical features to help in patient risk stratification. This study aimed to investigate the association between genomic alterations and prognosis in children with JMML. Genomic DNA was extracted from a total of 93 patients with JMML for targeted sequencing. Univariable and multivariable analysis were used to evaluate the correlation between gene mutations and prognosis of the patients. Patients with PTPN11 mutation exhibited significantly lower event-free survival (EFS) compared with non-PTPN11 mutations (P = 0.005). Patients without or with one somatic alteration at diagnosis showed significantly better prognosis in comparison with those with more than two alterations (P = 0.009). PTPN11 mutation with additional alterations showed significantly the poorest outcome in comparison with those with only one non-PTPN11 mutation, only one PTPN11 mutation, and combined mutations without PTPN11, respectively (P < 0.0001).Conclusion: Both PTPN11 mutation and the number of somatic alterations detected at diagnosis are likely to be the major determinant of outcome in JMML. The subgroup of patients with PTPN11 mutation showed the shortest survival which was even worsened when a secondary mutation was present.

Immunophenotypic characteristics of juvenile myelomonocytic leukaemia and their relation with the molecular subgroups of the disease

“…PTPN11 was the most frequent finding, as has already been described by other groups 3,7,37 . As distinct clinical presentations and outcomes have been described for each mutation, we tried to determine if they also have different phenotypic features 6,10,38,39 . There were only a few patients in each subgroup, but patients with PTPN11 and NF1 had a larger increase in CD34/CD117 + cells, and were the only groups presenting expression of CD7 in myeloid progenitors.…”

“…3,7,37 As distinct clinical presentations and outcomes have been described for each mutation, we tried to determine if they also have different phenotypic features. 6,10,38,39 There were only a few patients in each subgroup, but patients with PTPN11 and NF1 had a larger increase in CD34/CD117 + cells, and were the only groups presenting expression of CD7 in myeloid progenitors. The highest percentages of classical monocytes were observed in NF1 and NRAS and that of intermediate forms were more abundant in PTPN11 and KRAS.…”

Acute myeloid leukaemia with myelodysplasia-related change in a child living with human immunodeficiency virus infection, a transformation from underlying juvenile myelomonocytic leukaemia

“…This has been described in JMML where it is proposed to play a role in disease progression (rather than functioning as a driver mutation). 2,9,12,13 SETBP1 mutations have been associated with poor outcome. 1,9,14 Most patients with JMML (65%) have a normal karyotype 5,15 whilst monosomy 7 and other abnormalities are found in 25% and 10% of cases, respectively.…”

“…2,9,12,13 SETBP1 mutations have been associated with poor outcome. 1,9,14 Most patients with JMML (65%) have a normal karyotype 5,15 whilst monosomy 7 and other abnormalities are found in 25% and 10% of cases, respectively. 5 Allogeneic HSCT offers the best curative option with an event-free survival of about 52%.…”

Four‐year remission despite umbilical cord graft rejection in juvenile myelomonocytic leukemia with PTPN11 mutations

“…In general, patients with somatic PTPN11 mutations have poor prognoses without HSCT. 2,3 A 2-month-old infant was referred to our hospital because of fever and repeated skin infections. A complete blood cell count showed…”