Genetic Variants in Pediatric Myeloproliferative Neoplasms Revealed by Next Generation Sequencing.

Abstract

Background: Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells that include BCR::ABL1-negative MPNs such as essential thrombocythemia (ET) and primary myelofibrosis (PMF). MPNs are rare in children, and knowledge of the genetics and biology of pediatric MPNs is very limited. Here, we report genetic variants in pediatric MPNs revealed by next generation sequencing (NGS).

Methods: The study included nine pediatric patients (eight with ET and one with PMF) consecutively diagnosed between January 2000 and June 2023. NGS was performed on an Ion S5 XL Sequencer with the OncomineTM myeloid research assay using bone marrow aspirate samples.

Results: Five patients (56%) had clinically significant genetic variants. Two patients with ET had JAK2 V617F (driver) and two patients with ET had FLT3 E656A and ETV6 I10V, respectively. A single patient with PMF had 10 variants in eight genes, including two previously reported nonsense variants (ASXL1 W960* and TET2 R1452*) and three novel variants (BCOR A997E, TET2 I2002Mfs*12, and ZRSR2 F86_E102del). Of all, one patient (11%) experienced an event of transient ischemic attack with visual loss for 5 minutes and one patient with PMF expired of septic shock four months after diagnosis.

Conclusions: The results suggest a different genetic profile in pediatric MPN, with a lower incidence of driver variants in pediatric ET and multiple non-driver variants with poor prognostic implications in pediatric PMF.