Genetic Variants in Pediatric Myeloproliferative Neoplasms Revealed by Next Generation Sequencing

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Myeloproliferative neoplasms (MPNs) are rare clonal disorders of hematopoietic stem cells.
• Pediatric MPNs, including essential thrombocythemia (ET) and primary myelofibrosis (PMF), have limited genetic and biological understanding.
• Next-generation sequencing (NGS) offers a powerful tool to investigate the genetic landscape of pediatric MPNs.

Purpose of the Study:

• To identify and characterize genetic variants in pediatric MPNs using NGS.
• To explore the genetic differences between pediatric and adult MPNs.
• To assess the clinical significance of identified genetic variants in pediatric MPN patients.

Main Methods:

• Nine pediatric patients (8 ET, 1 PMF) diagnosed between 2000-2023 were included.
• Bone marrow aspirate samples were analyzed using next-generation sequencing (NGS) on an Ion S5 XL Sequencer.
• The OncomineTM myeloid research assay was employed for comprehensive genetic variant detection.

Main Results:

• Clinically significant genetic variants were identified in 56% of pediatric MPN patients.
• Two ET patients harbored the JAK2 V617F driver mutation; two others had FLT3 and ETV6 variants.
• The single PMF patient exhibited 10 variants across eight genes, including novel mutations in BCOR, TET2, and ZRSR2.

Conclusions:

• Pediatric MPNs present a distinct genetic profile compared to adult forms.
• Pediatric ET shows a lower incidence of common driver mutations.
• Pediatric PMF is characterized by multiple non-driver variants, potentially indicating a poorer prognosis.