Juvenile Myelomonocytic Leukemia (JMML) is a rare myeloproliferative disease of childhood, recognized as an entity involving genes from the RAS-MAPK pathway. In JMML, Immunophenotyping (FCI) has been used for blast counting and evaluation of monocyte subtypes. It is controversy if this distribution is similar to that seen in Chronic Myelomonocytic Leukemia (CMML). Recently, we have reported a study on immunophenotyping in JMML at diagnosis.

To expand the immunophenotypic analysis, studying erythroid and monocytic maturation.

8-color antibody combinations were used, including CD64, IREM2, CD105, CD36 and CD71 in the previous panel. FCI findings were correlated with patients’ molecular profile.

52 JMML patients were evaluated: median age 17-months. PTPN11 (13) and KRAS (11) mutations were more frequent. Patients with CBL mutation, together with NRAS and KRAS subgroups were younger (p=0.026). Decrease of hematogones type I (median 0.6%) and T lymphocytes (median 3.4%), increase CD34+CD117+ (3.4%) and monocytes (12.2%) were similar between molecular subgroups. Abnormal expression of CD7 in myeloid progenitors was more frequent in PTPN11 patients. Erythroid and monocytic precursors were assessed in 24 patients. Monoblasts had a median of 14.9% and promonocyte were 29.5%, with higher percentages in NF1 and PTPN11 subgroups. Patients with NRAS, NF1 and absence of RAS mutations showed a low percentage of CD16+ monocytes and a higher percentage of CD14+CD16- monocytes (classical), similar to CMML, while PTPN11, KRAS and CBL patients had lower percentages of classical monocytes as found in MDS (p=0.02).

We confirmed our previous results. CBL subgroup had similar features as other molecular profiles. JMML patients presented an increase of myeloblasts and early monocytic precursors, compatible with a more aggressive disease, intermediary between a chronic myeloid neoplasm and a progression to acute leukemia, more evident in PTPN11 and NF1 mutated patients. Despite examined in bone marrow, monocytes subsets analysis don´t seem to be a diagnostic strategy for JMML. The features of FCI data should also be compared with the methylation profile.