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MPL is the receptor that tells the bone marrow to make platelets. Romiplostim and eltrombopag switch it on to raise platelet counts; in some myeloproliferative neoplasms a mutant partner protein, calreticulin, grips it and keeps it on.
MPL (chromosome 1p34.2) is the thrombopoietin receptor that regulates haematopoietic stem cell renewal, megakaryocyte differentiation and platelet formation; thrombopoietin binding triggers rapid JAK2 phosphorylation and docking of STAT5, SHIP, GRB2, SOS1 and PI3K, and the cascades that follow drive megakaryocyte proliferation, survival and differentiation (UniProt P40238). In OnCo it is the receptor that the TPO agonists romiplostim (a peptide fused to an antibody Fc fragment) and eltrombopag (a small molecule binding the transmembrane region) activate; the receptor that frameshift-mutant calreticulin binds and activates in CALR-mutant essential thrombocythaemia and primary myelofibrosis, which the antibody INCA033989 blocks; and one of the three drivers (JAK2, CALR, MPL) that ruxolitinib acts regardless of.
In plain words · MPL is the receptor that tells the bone marrow to make platelets. Romiplostim and eltrombopag switch it on to raise platelet counts; in some myeloproliferative neoplasms a mutant partner protein, calreticulin, grips it and keeps it on.
MPL is the receptor that tells the bone marrow to make platelets. Romiplostim and eltrombopag switch it on to raise platelet counts; in some myeloproliferative neoplasms a mutant partner protein, calreticulin, grips it and keeps it on.
MPL has no kinase of its own and signals through JAK2, so JAK inhibitors act below it whatever the driver.
2 products aim at MPL (thrombopoietin receptor): small molecules. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Tumour-associated overexpression: 1 antibody (Romiplostim) aim at the antigen, which HPA finds with no normal tissue stained high; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA MPL: RNA low tissue specificity; blood lineage lineage enriched (granulocytes 1 nTPM); no normal tissue stained high. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia); Open Targets associates it with 2 specific cancer types at or above 0.5 (primary myelofibrosis, essential thrombocythemia). (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas MPL tissue; Human Protein Atlas MPL pathology; Open Targets ENSG00000117400 associations
First described 1992. Earliest sequence paper UniProt cites for the protein: Vigon et al, Proc. Natl. Acad. Sci. U.S.A, 1992, "Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily". Source.
MPL has no kinase of its own and signals through JAK2, so JAK inhibitors act below it whatever the driver. The INCA033989 record explains that CALR frameshift mutations give the protein a positively charged tail that lets it bind and activate MPL on the cell surface, switching on JAK-STAT signalling without thrombopoietin.
RNA: low tissue specificity, detected in some normal tissues. Blood: lineage enriched (granulocytes 1 nTPM).
No normal tissue stained high.
No cancer sample stained medium or high.
HPA MPL tissue · HPA MPL pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Eltrombopag is a daily tablet that raises platelet counts by stimulating the bone marrow; it is approved for immune thrombocytopenia and severe aplastic anaemia, and haematologists also use it when low platelets complicate blood cancers and their treatment.
Romiplostim is a weekly injection that tells the bone marrow to make more platelets; it is approved for immune thrombocytopenia and for radiation injury, and is being tested for the low platelets that chemotherapy causes.
Query for this target: (TITLE:"MPL" OR ABSTRACT:"MPL" OR TITLE:"thrombopoietin receptor" OR ABSTRACT:"thrombopoietin receptor" OR TITLE:"TPO receptor" OR ABSTRACT:"TPO receptor" OR TITLE:"TPOR" OR ABSTRACT:"TPOR" OR TITLE:"THPOR" OR ABSTRACT:"THPOR" OR TITLE:"CD110" OR ABSTRACT:"CD110") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MPL (thrombopoietin receptor), not a curated reading list.
Shares JAK-STAT signalling, JAK2, Ruxolitinib, Myeloproliferative neoplasms (PV, ET, myelofibrosis) and the tag wave5-target.
Shares JAK-STAT signalling, JAK2, Myeloproliferative neoplasms (PV, ET, myelofibrosis) and the tag wave5-target.
Shares JAK2 and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.