JAK2 V617F mutation is a rare event in juvenile myelomonocytic leukemia

Abstract

Taken together, the data reported by Cazzaniga et al. and our results consistently show that in pediatric patients, NPM1 mutations are less common than in adults and tend to affect older patients. Preliminary data also indicate that NPM1 mutations might be associated with favorable outcome, which warrants further studies to address this question. In addition, our results point to an effect of age on the prevalence of different NPM1-mutations, with non-typical (i.e. non-type A) mutations being most prevalent in children and younger adults. The reason for this association is unknown, but might refer to different molecular mechanisms involved in the development of this abnormality, a process which is currently largely unclear. This finding has also important implications for the MRD analysis and molecular follow-up of pediatric cases with NPM1 þ AML. Whereas in adults, type A mutations predominate and assays focusing on this type will be suitable in most cases, in pediatric patients mutations should always be analyzed by sequencing. In these cases, a recently reported LNA-based procedure might be advantageous for follow-up of residual disease after treatment.

RAS diseases in children

“…Mutations were often subclonal and were involved in the progression of leukemia.82 Genetic alterations in SRFS2, TET2, RUNX1, JAK2 and ASXL1 do not play a significant role in JMML. 51,75,[83][84][85][86] Similarly, inactivation of the TP53 tumor suppressor gene and internal tandem duplication and activation of the Fms-like tyrosine kinase 3 (FLT3) gene are generally absent in JMML. 87,88 With the paucity of genetic lesions, epigenetic changes such as abnormal DNA methylation pattern are of particular interest.…”

Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia

“…75,76 Additionally, mutations common in other myeloid diseases such as FLT3 and JAK2 are rarely, if ever, found in JMML. 77,78 JMMLFdiagnosis, clinical course and treatment…”

The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms

“…Homozygous JAK2V617F mutations are present in 24% to 27% of patients with PV, 3% to 4% of patients with ET, and 6% to 18% of patients with CIMF [24][25][26][27][28][29][30][31]. The JAK2V617F mutation was also found in patients with nonclassic MPN, although in much lower frequency: less than 20% of patients with aCML, less than 5% of patients with chronic myelomonocytic leukemia (CMML), less than 20% of patients with juvenile myelomonocytic leukemia (JMML) about 5% of patients with MDS, and rarely in patients with systemic mastocytosis [32][33][34][35][36][37]. Most MDS patients that did exhibit a JAK2 mutation were diagnosed with the provisional diagnosis of refractory anemia with ringed sideroblasts and associated with marked thrombocytosis (RARS-T), which falls under the MDS/MPN-unclassifiable category.…”