MPLGene

In 1990, an oncogene called v-mpl, from mouse myeloproliferative leukemia virus, capable of immortalizing bone marrow hematopoietic cells from different lineages, was identified. In 1992, the human homologue to this oncogene, cloned with the name c-mpl.

The MPL gene (MLP is the acronym for Myeloproliferative Leukemia Protein) is a protein-coding gene
locatedon chromosome1p34
.2. The gene encodes the receptor protein TPO-R (CD110), which has homology to members of the hematopoietic receptor superfamily. The ligand for the MPL receptor protein is thrombopoietin (thrombopoietin was cloned in 1994). Thrombopoietin is the master regulator of megakaryocytopoiesis and platelet formation.

TPO-R consists of a 635 amino acid transmembrane domain with two extracellular cytokine receptor domains and two intracellular cytokine receptor domains. TPO-R-deficient mice become thrombocytopenic. An important paralog of the MPL gene is EPOR.

List of diseases associated with mutations in TPO-R:

• Disease-causing germline mutation(s) Thrombocytosis, familial (ORPHA:71493)
• Disease-causing germline mutation(s) (loss of function) Congenital amegakaryocytic thrombocytopenia (ORPHA:3319)
• Disease-causing germline mutation(s) (loss of function) Hereditary aplastic anemia, isolated form (ORPHA:397692)
• Disease-causing somatic mutation(s) Essential thrombocythemia (ORPHA:3318)
• Disease-causing somatic mutation(s) Polycythaemia vera (ORPHA:729)
• Disease-causing somatic mutation(s) Primary myelofibrosis (ORPHA:824)

1. Kim SY et al (2015) CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. Am J Clin Pathol 143:635-644.
2. Vainchenker W et al (2017) Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood 129:667-679.