RESUMEN
INTRODUCTION: Juvenile myelomonocytic leukemia (JMML) is a rare clonal myelodysplastic/myeloproliferative neoplasm of early childhood. Historically, it was difficult to diagnose clinically, as patients present with manifestations shared with other hematologic malignancies or viral infections. It is now clear that JMML is a disease of hyperactive RAS signaling. PATIENTS AND METHODS: We examined the bone marrow of 41 Egyptian children with JMML by direct sequencing for mutations in the RAS pathway genes. RESULTS: Mutations were detected in 33 (80%) of 41 patients. We identified 12 (29%) of 41 patients with PTPN11 mutation; 18 (44%) of 41 with RAS mutation; 9 (22%) of 41 with NRAS mutation; 9 (22%) of 41 with KRAS mutation; and 3 (7%) of 41 with CBL mutation. Eleven (92%) of the PTPN11 mutations were detected in exon 3 and 1 (8%) in exon 13. Seven of the NRAS mutations were in exon 2, and 2 were in exon 3. All KRAS mutations were in exon 2. The 3 cases with CBL mutation were homozygous mutations in exon 8. All the mutations detected in PTPN11, NRAS/KRAS, and the CBL genes were previously reported missense mutations in JMML. CONCLUSION: Our results demonstrate that Egyptian children diagnosed with JMML have high frequency of NRAS/KRAS mutations and lower frequency of PTPN11 mutations as compared with previous studies. The concept of mutually exclusive RAS pathway mutations was clearly observed in our patients. All cancer centers in our region should start implementing molecular diagnostic methods before confirming the diagnosis of JMML and before offering hematopoietic stem cell transplantation.