Distinct molecular abnormalities underlie unique clinical features of essential thrombocythemia in children

Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis

“…X chromosome inactivation studies in girls with triple negative disease argued against clonal disease . However, targeted deep sequencing performed in two cohorts of children with ET revealed that 32–40% of those lacking JAK2 , MPL , or CALR mutations had somatic changes in one or more other genes previously implicated in myeloproliferative neoplasms . In these triple negative cases, any given other gene (e.g., ASXL1 and IRF8 ) was mutated in just a few patients.…”

“…[5] However, targeted deep sequencing performed in two cohorts of children with ET revealed that 32-40% of those lacking JAK2, MPL, or CALR mutations had somatic changes in one or more other genes previously implicated in myeloproliferative neoplasms. [6,7] In these triple negative cases, any given other gene (e.g., ASXL1 and IRF8) was mutated in just a few patients. Thus, the diagnosis of ET in children remains challenging and the possibility remains that other genes may underlie the thrombocytosis.…”

Bone marrow histology for the diagnosis of essential thrombocythemia in children: a multicenter Italian study

“…14,15 Moreover, another large study about pediatric ET did not specifically address BM importance. 16 Our study is seemingly the largest published study on BM histology in pediatric patients with clinically diagnosed ET to date. Among 21 children, 20 cases had BM findings consistent with MPN (ET: n 5 16; PV: n 5 1; pre-PMF: n 5 3) and 1 3NEG case had a histological picture of ST.…”

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

“…Although the primary drivers of adult MPNs are well established, the molecular pathogeneisis in children is largely unkown, and some studies suggest higher rates of "triple-negative" disease ( Figure 6). 94,[97][98][99] This underscores the importance of identifying appropriate diagnostic criteria for use in pediatrics-while the WHO criteria may be appropriate for adults, they likely cannot be applied to children, who are more frequently triple negative and have different normal values than adults for certain blood counts, including red blood cell (RBC) count, Hb, and hematocrit (Hct), which vary with age. 100 Eight children with a JAK2 V617F -mutated MPN were examined to see if their type of MPN could be clearly discerned.…”