MPL (thrombopoietin receptor)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
MPL has no kinase of its own and signals through JAK2, so JAK inhibitors act below it whatever the driver.
- 3 · How drugs use it
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.
External identifiers
Biology
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.
- Megakaryocytes and haematopoietic stem cells
- Essential thrombocythaemia and primary myelofibrosis (MPL as driver; CALR-mutant activation)
- Thrombocytopenia in AML and MDS (TPO agonist use in the corpus records)
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.
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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.
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