Analysis of genes encoding epigenetic regulators in myeloproliferative neoplasms: Coexistence of a novel SETBP1 mutation in a patient with a p.V617F JAK2 positive myelofibrosis

Abstract

In recent years it has been shown that the causes of chronic myeloproliferative neoplasms (MPNs) are more complex than a simple signaling aberration and many other mutated genes affecting different cell processes have been described. For instance, mutations in genes encoding epigenetic regulators are more frequent than expected. One of the latest genes described as mutated is SET binding protein 1 (SETBP1). In silico tools have revealed that there are several human SETBP1 paralogous to nuclear receptor binding SET domain protein 1 (NSD1), NSD2 and NSD3, for example, which are also involved in the development of other hematological malignancies. Therefore, the present study analyzed the mutational status of NSD1, NSD2, NSD3 and SETBP1 in BCR-ABL1 negative MPNs with or without Janus kinase 2 (JAK2) p.V617F mutation. The present study revealed that the NSD genes are not frequently mutated in MPNs. However, a novel SETBP1 mutation was identified in a patient with p.V617F JAK2 positive primary myelofibrosis. These results provide further insight into the genetic complexity of MPNs.

Coexistence of Primary Myelofibrosis and Paroxysmal Nocturnal Hemoglobinuria Clone with JAK2 V617F, U2AF1 and SETBP1 Mutations: A Case Report and Brief Review of Literature

“…The U2AF1 mutations were observed in 9.3–16% of PMF patients [ 3 , 21 ] and it is known to be associated with poor survival [ 22 , 23 ]. On the other hand, the SETBP1 mutation is rare in PMF patients (0.3–2.4%) [ 3 , 6 , 24 , 25 ], while SETBP1 was identified in atypical chronic myelogenous leukemia (CML) with a frequency of 32% [ 24 ]. One report states that increased SETBP1 gene expression is associated with a progression from PMF to acute myeloid leukemia (AML) [ 26 ].…”