Clinical Information

DNA sequence variants in exon 10 of the myeloproliferative leukemia virus oncogene (MPL) have been detected in approximately 5% of patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), which are hematopoietic neoplasms classified within the broad category of myeloproliferative neoplasms. MPL codes for a transmembrane tyrosine kinase, and the most common MPL variants are single base pair substitutions at codon 515. These alterations have been shown to promote constitutive, cytokine-independent activation of the JAK/STAT signaling pathway and contribute to the oncogenic phenotype. At least 8 different MPL exon 10 variants have been identified in PMF and ET to date, and variants outside of exon 10 have not yet been reported. The vast majority of MPL variants have been found in specimens testing negative for the most common variant identified in myeloproliferative neoplasms, JAK2 V716F, although a small number of cases with both types of variants have been reported. MPL variants have not been identified in patients with polycythemia vera, chronic myelogenous leukemia, or other myeloid neoplasms.

Identification of MPL variants can aid in the diagnosis of a myeloproliferative neoplasm and is highly suggestive of either PMF or ET.