MPL

Summary

Gene Symbol: MPL
Description: MPL proto-oncogene, thrombopoietin receptor
Alias: C-MPL, CD110, MPLV, THCYT2, TPOR, thrombopoietin receptor, TPO-R, myeloproliferative leukemia protein, myeloproliferative leukemia virus oncogene, proto-oncogene c-Mpl
Species: human
Products:     MPL

Top Publications

  1. Kiladjian J, Cervantes F, Leebeek F, Marzac C, Cassinat B, Chevret S, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008;111:4922-9 pubmed publisher
    ..Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome...
  2. Chaligne R, James C, Tonetti C, Besancenot R, Le Couedic J, Fava F, et al. Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis. Blood. 2007;110:3735-43 pubmed
    The MPL (W515L and W515K) mutations have been detected in granulocytes of patients suffering from certain types of primitive myelofibrosis (PMF)...
  3. Guglielmelli P, Pancrazzi A, Bergamaschi G, Rosti V, Villani L, Antonioli E, et al. Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol. 2007;137:244-7 pubmed
    The clinical and haematological phenotype of patients with myelofibrosis harbouring MPL(W515L/K) mutation has not been thoroughly investigated. Of 217 myelofibrosis subjects, 18 (8...
  4. Patnaik M, Lasho T, Finke C, Gangat N, Caramazza D, Siragusa S, et al. MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms. Leukemia. 2010;24:859-60 pubmed publisher
  5. Hu W, Zhao Y, Ishii T, Sozer S, Shi J, Zhang W, et al. Haematopoietic cell lineage distribution of MPLW515L/K mutations in patients with idiopathic myelofibrosis. Br J Haematol. 2007;137:378-9 pubmed
  6. Teofili L, Giona F, Torti L, Cenci T, Ricerca B, Rumi C, et al. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica. 2010;95:65-70 pubmed publisher
    Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia...
  7. Ballmaier M, Germeshausen M, Schulze H, Cherkaoui K, Lang S, Gaudig A, et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood. 2001;97:139-46 pubmed
    ..Flow cytometric analysis revealed absent surface expression of the TPO receptor c-Mpl in 3 of 3 patients...
  8. Pardanani A, Levine R, Lasho T, Pikman Y, Mesa R, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108:3472-6 pubmed
    Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM)...
  9. Moliterno A, Williams D, Gutierrez Alamillo L, Salvatori R, Ingersoll R, Spivak J. Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci U S A. 2004;101:11444-7 pubmed
    ..We have reported defective thrombopoietin receptor (Mpl) protein expression in MPD patients...

More Information

Publications85

  1. Pardanani A, Lasho T, Finke C, Markovic S, Tefferi A. Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T lymphocytes. Leukemia. 2007;21:2206-7 pubmed
  2. Tefferi A. JAK and MPL mutations in myeloid malignancies. Leuk Lymphoma. 2008;49:388-97 pubmed publisher
    ..JAK3 is important in lymphoid and JAK2 in myeloid cell proliferation and differentiation. The thrombopoietin receptor MPL is one of several JAK2 cognate receptors and is essential for myelopoiesis in general and ..
  3. Chaligne R, Tonetti C, Besancenot R, Roy L, Marty C, Mossuz P, et al. New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition. Leukemia. 2008;22:1557-66 pubmed publisher
    MPL (or thrombopoietin receptor, TPO-R) 515 mutations have recently been described in 5-10% of primitive myelofibrosis (PMF) cases as decisive oncogenic events capable of triggering the disease...
  4. Kilpivaara O, Levine R. JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia. 2008;22:1813-7 pubmed publisher
    ..MPN, genomic studies have identified JAK2 exon 12 mutations in JAK2V617F-negative PV and activating mutations in MPL in patients with JAK2V617F-negative ET and PMF...
  5. Abe M, Suzuki K, Inagaki O, Sassa S, Shikama H. A novel MPL point mutation resulting in thrombopoietin-independent activation. Leukemia. 2002;16:1500-6 pubmed
    Thrombopoietin (TPO) and its receptor (MPL) are important regulators of megakaryopoiesis. MPL belongs to a cytokine receptor superfamily...
  6. Drachman J, Kaushansky K. Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain. Proc Natl Acad Sci U S A. 1997;94:2350-5 pubmed
    Thrombopoietin (TPO) acts through its receptor, Mpl, to stimulate the proliferation and maturation of megakaryocytes and their progenitors...
  7. Matthews E, Thévenin D, Rogers J, Gotow L, Lira P, Reiter L, et al. Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation. FASEB J. 2011;25:2234-44 pubmed publisher
    ..rotational variations in transmembrane (TM) helix interactions participate in the activity states of the thrombopoietin receptor (TpoR), a type 1 cytokine receptor that controls the production of blood platelets...
  8. Mignotte V, Vigon I, Boucher de Crèvecoeur E, Romeo P, Lemarchandel V, Chretien S. Structure and transcription of the human c-mpl gene (MPL). Genomics. 1994;20:5-12 pubmed
    The human c-mpl proto-oncogene encodes a member of the cytokine receptor superfamily, expressed mainly in CD 34-positive hematopoietic progenitors and in the megakaryocytic lineage...
  9. Souyri M, Vigon I, Penciolelli J, Heard J, Tambourin P, Wendling F. A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors. Cell. 1990;63:1137-47 pubmed
    The myeloproliferative leukemia virus (MPLV) is an acute leukemogenic murine replication-defective retrovirus...
  10. Schnittger S, Bacher U, Haferlach C, Beelen D, Bojko P, Bürkle D, et al. Characterization of 35 new cases with four different MPLW515 mutations and essential thrombocytosis or primary myelofibrosis. Haematologica. 2009;94:141-4 pubmed publisher
  11. Vannucchi A, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112:844-7 pubmed publisher
    ..MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients...
  12. Tijssen M, di Summa F, van den Oudenrijn S, Zwaginga J, van der Schoot C, Voermans C, et al. Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia. Br J Haematol. 2008;141:808-13 pubmed publisher
    ..Genetic defects in the gene encoding the thrombopoietin (Tpo) receptor, MPL, are the cause of this disease...
  13. Liu K, Martini M, Rocca B, Amos C, Teofili L, Giona F, et al. Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia. Haematologica. 2009;94:1368-74 pubmed publisher
    ..Germ line mutations have been identified in the genes for thrombopoietin (THPO) and its receptor, MPL. A clustering of familial cases with the MPL-G1073A mutation that results in a serine to asparagine substitution (..
  14. Pecquet C, Staerk J, Chaligne R, Goss V, Lee K, Zhang X, et al. Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor. Blood. 2010;115:1037-48 pubmed publisher
    Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs)...
  15. Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost. 2011;37:673-81 pubmed publisher
    ..In most of the cases the disease is caused by homozygous or compound heterozygous mutations in the gene MPL encoding the receptor for the hematopoietic growth factor thrombopoietin...
  16. Pikman Y, Lee B, Mercher T, McDowell E, Ebert B, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:e270 pubmed
    ..in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte-colony stimulating factor receptor (GCSFR)...
  17. de Sauvage F, Hass P, Spencer S, Malloy B, Gurney A, Spencer S, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature. 1994;369:533-8 pubmed
    ..This protein binds to and activates the c-mpl protein, a member of the cytokine receptor superfamily...
  18. Williams D, Kim A, Rogers O, Spivak J, Moliterno A. Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis. Exp Hematol. 2007;35:1641-6 pubmed
    ..IMF), are characterized by a spectrum of clinical features and linked by common genetic lesions in JAK2 and MPL. However, the clinical phenotypes in genetically undefined MPD patients are similar to those patients with JAK2 and ..
  19. Vigon I, Mornon J, Cocault L, Mitjavila M, Tambourin P, Gisselbrecht S, et al. 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. Proc Natl Acad Sci U S A. 1992;89:5640-4 pubmed
    We have cloned the human homolog of the v-mpl oncogene transduced in the myeloproliferative leukemia retrovirus, which presents striking homologies with members of the hematopoietin receptor superfamily...
  20. Lee T, Kantarjian H, Ma W, Yeh C, Giles F, Albitar M. Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling. PLoS ONE. 2011;6:e23396 pubmed publisher
    Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures...
  21. Germeshausen M, Ballmaier M, Welte K. MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Hum Mutat. 2006;27:296 pubmed
    ..Mutations in the gene for the thrombopoietin receptor MPL were defined as the molecular cause in CAMT patients...
  22. Martinón Torres N, Vázquez Donsión M, Loidi L, Couselo J. CAMT in a female with developmental delay, facial malformations and central nervous system anomalies. Pediatr Blood Cancer. 2011;56:452-3 pubmed publisher
    ..It is caused by mutations in the thrombopoietin receptor gene, c-mpl, involved in the proliferation and differentiation of megakaryocytes and platelets...
  23. Ihara K, Ishii E, Eguchi M, Takada H, Suminoe A, Good R, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci U S A. 1999;96:3132-6 pubmed
    ..Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency...
  24. Ding J, Komatsu H, Wakita A, Kato Uranishi M, Ito M, Satoh A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood. 2004;103:4198-200 pubmed
    ..point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family...
  25. El Harith E, Roesl C, Ballmaier M, Germeshausen M, Frye Boukhriss H, von Neuhoff N, et al. Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene. Br J Haematol. 2009;144:185-94 pubmed publisher
    ..germline mutations in the myeloproliferative leukaemia virus oncogene gene (MPL), which codes for the thrombopoietin receptor MPL...
  26. Miyakawa Y, Rojnuckarin P, Habib T, Kaushansky K. Thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes. J Biol Chem. 2001;276:2494-502 pubmed
    ..The hormone acts by binding to the Mpl receptor, the product of the cellular proto-oncogene c-mpl...
  27. Ding J, Komatsu H, Iida S, Yano H, Kusumoto S, Inagaki A, et al. The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity. Blood. 2009;114:3325-8 pubmed publisher
    ..activating mutation (Asn505) in the transmembrane domain (TMD) of c-MPL, which encodes the thrombopoietin receptor, caused familial essential thrombocythemia...
  28. Hussein K, Bock O, Theophile K, Schulz Bischof K, Porwit A, Schlue J, et al. MPLW515L mutation in acute megakaryoblastic leukaemia. Leukemia. 2009;23:852-5 pubmed publisher
    The thrombopoietin receptor gene (MPL) is expressed in megakaryocytes and exhibits the gain of function point mutation W515K/L in approximately 5% of patients with primary myelofibrosis/idiopathic myelofibrosis (PMF) representing one ..
  29. Beer P, Campbell P, Scott L, Bench A, Erber W, Bareford D, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood. 2008;112:141-9 pubmed publisher
    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear...
  30. Bal G, Fabian D, Maia D, Ringel F, Salama A. Effect of thrombopoietin receptor agonists on leukocyte and haematopoietic stem and progenitor cells in the peripheral blood of patients with immune thrombocytopenic purpura. Ann Hematol. 2017;96:2045-2056 pubmed publisher
    The thrombopoietin receptor agonists (TPO-RAs), romiplostim and eltrombopag, stimulate megakaryopoiesis and thereby increase platelet counts. Both drugs are increasingly used in the treatment of immune thrombocytopenic purpura (ITP)...
  31. Wang J, Hao J, He N, Ji C, Ma D. The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia. Turk J Haematol. 2016;33:180-6 pubmed publisher
    ..CALR mutations were described recently in Janus kinase 2 gene (JAK2)-negative or MPL-negative primary myelofibrosis (PMF) and essential thrombocythemia (ET) patients...
  32. dos Santos M, Mitne Neto M, Miyashiro K, Chauffaille M, Rizzatti E. Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms. J Clin Pathol. 2014;67:176-8 pubmed publisher
    ..4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN. ..
  33. Moulis G, Lapeyre Mestre M, Adoue D, Sailler L. [Epidemiology and pharmacoepidemiology of immune thrombocytopenia]. Rev Med Interne. 2017;38:444-449 pubmed publisher
    ..Exposure to splenectomy decreases while rituximab and thrombopoietin receptor agonists (TPO-RA) are the most used second-line drugs for persistent ITP...
  34. Koka P, Kitchen C, Reddy S. Targeting c-Mpl for revival of human immunodeficiency virus type 1-induced hematopoietic inhibition when CD34+ progenitor cells are re-engrafted into a fresh stromal microenvironment in vivo. J Virol. 2004;78:11385-92 pubmed
    ..Thy/Liv) due to human immunodeficiency virus type 1 (HIV-1) infection is also accompanied by a severe loss of c-Mpl expression on these progenitor cells...
  35. Alvarez D, Agaisse H. The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles. Infect Immun. 2016;84:1806-1814 pubmed publisher
    ..Here we investigated the role of the metalloprotease Mpl in the dissemination process...
  36. Han Y, Yue L, Wei M, Ren X, Shao Z, Zhang L, et al. Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis. PLoS ONE. 2017;12:e0166014 pubmed publisher
    ..In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow...
  37. Comont T, Tavitian S, Bardiaux L, Fort M, Debiol B, Morère D, et al. Platelet transfusion refractoriness in patients with acute myeloid leukemia treated by intensive chemotherapy. Leuk Res. 2017;61:62-67 pubmed publisher
    ..5days. HLA-matched transfusions induced a significant increment in platelet counts in 37% of cases. Thrombopoietin receptor agonists were given to 10 patients but did not shorten the duration of thrombocytopenia, reduce severe ..
  38. Wijekoon H, Toyota K, Kim S, Fang J, Bwalya E, Hosoya K, et al. Differentiation potential of synoviocytes derived from joints with cranial cruciate ligament rupture and medial patella luxation in dogs. Res Vet Sci. 2017;114:370-377 pubmed publisher
    ..Cranial cruciate ligament ruptured (CCLr) (n=12) and medial patella luxated (MPL) (n=10) knee joints of the dogs were used to collect the synovial membrane (SM)...
  39. Lin C, Kaushansky K, Zhan H. JAK2V617F-mutant vascular niche contributes to JAK2V617F clonal expansion in myeloproliferative neoplasms. Blood Cells Mol Dis. 2016;62:42-48 pubmed publisher
    ..In addition, the thrombopoietin (TPO) receptor MPL is up regulated in JAK2V617F ECs and contributes to the maintenance/expansion of the JAK2V617F..
  40. Rosso V, Petiti J, Bracco E, Pedrola R, Carnuccio F, Signorino E, et al. A novel assay to detect calreticulin mutations in myeloproliferative neoplasms. Oncotarget. 2017;8:6399-6405 pubmed publisher
    ..Most Ph negative cases have an activating JAK2 or MPL mutation...
  41. Marty C, Chaligne R, Lacout C, Constantinescu S, Vainchenker W, Villeval J. Ligand-independent thrombopoietin mutant receptor requires cell surface localization for endogenous activity. J Biol Chem. 2009;284:11781-91 pubmed publisher
    The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia...
  42. Kuwaki T, Oda A, Yuki C, Suzuki H, Murasaki K, Fujita H, et al. Lineage-specific expression of granulocyte colony-stimulating factor and thrombopoietin receptors in terminally differentiated hematopoietic cells. Exp Hematol. 2006;34:1651-4 pubmed
  43. Pavlov I, Hadjiev E, Alaikov T, Spassova S, Stoimenov A, Naumova E, et al. Calreticulin Mutations in Bulgarian MPN Patients. Pathol Oncol Res. 2018;24:171-174 pubmed publisher
    Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs)...
  44. Bellanne Chantelot C, Mosca M, Marty C, Favier R, Vainchenker W, Plo I. Identification of MPL R102P Mutation in Hereditary Thrombocytosis. Front Endocrinol (Lausanne). 2017;8:235 pubmed publisher
    ..molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis...
  45. Oliva E, Alati C, Santini V, Poloni A, Molteni A, Niscola P, et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 2017;4:e127-e136 pubmed publisher
    ..We tested whether eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and ..
  46. Sundell I, Koka P. Thrombocytopenia in HIV infection: impairment of platelet formation and loss correlates with increased c-Mpl and ligand thrombopoietin expression. Curr HIV Res. 2006;4:107-16 pubmed
    ..In HIV infected patients, both the serum thrombopoietin (TPO) levels and theTPO-c-Mpl complexes on the platelet surface were significantly elevated...
  47. Chang Y, Lin H, Chiang Y, Chen C, Huang L, Wang W, et al. Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms. Med Oncol. 2017;34:83 pubmed publisher
    Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN...
  48. Christiaansen A, Dixit U, Coler R, Marie Beckmann A, Reed S, Winokur P, et al. CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination. Vaccine. 2017;35:4255-4261 pubmed publisher
    ..ligand glucopyranosyl lipid adjuvant (GLA-SE), or SE with Salmonella minnesota-derived monophosphoryl lipid A (MPL-SE). Individuals were given 3 vaccine doses, on days 0, 28 and 168...
  49. Kotze A, Ruffell A, Lamb J, Elliott T. Response of drug-susceptible and -resistant Haemonchus contortus larvae to monepantel and abamectin alone or in combination in vitro. Vet Parasitol. 2018;249:57-62 pubmed publisher
    ..The resistance ratio was reduced from 12- to 3.2-fold when the two drugs were combined. The MPL-R isolate was resistant to both drugs, with resistance factors of 6-fold towards abamectin, and 10...
  50. Finazzi M, Carobbio A, Cervantes F, Isola I, Vannucchi A, Guglielmelli P, et al. CALR mutation, MPL mutation and triple negativity identify patients with the lowest vascular risk in primary myelofibrosis. Leukemia. 2015;29:1209-10 pubmed publisher
  51. Elf S, Abdelfattah N, Chen E, Perales Patón J, Rosen E, Ko A, et al. Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation. Cancer Discov. 2016;6:368-81 pubmed publisher
    ..We further show that the thrombopoietin receptor MPL is required for mutant CALR-driven transformation through JAK-STAT pathway activation, thus rendering ..
  52. Pancrazzi A, Guglielmelli P, Ponziani V, Bergamaschi G, Bosi A, Barosi G, et al. A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction. J Mol Diagn. 2008;10:435-41 pubmed publisher
    Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative ..
  53. Moradi Marjaneh R, Hassanian S, Fiuji H, Soleimanpour S, Ferns G, Avan A, et al. Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer. J Cell Physiol. 2017;: pubmed publisher
    ..this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
  54. Daly S, Conneally E, Langabeer S. Identification of MPL W515L/K mutations in patients with primary myelofibrosis and essential thrombocythaemia by allele-specific polymerase chain reaction. Acta Haematol. 2009;121:221-2 pubmed publisher
  55. Zhang X, Chuai Y, Nie W, Wang A, Dai G. Thrombopoietin receptor agonists for prevention and treatment of chemotherapy-induced thrombocytopenia in patients with solid tumours. Cochrane Database Syst Rev. 2017;11:CD012035 pubmed publisher
    ..Alternative interventions to platelet transfusion are limited. Different stages of preclinical and clinical studies have examined the thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid tumours.
  56. Hitchcock I, Chen M, King J, Kaushansky K. YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation. Blood. 2008;112:2222-31 pubmed publisher
    Thrombopoietin (Tpo), acting through the c-Mpl receptor, promotes the survival and proliferation of hematopoietic stem and progenitor cells and drives megakaryocyte differentiation...
  57. Kirito K. Effect of mutation on diagnosis, risk stratification, and treatment decisions in Philadelphia-negative myeloproliferative neoplasms. Rinsho Ketsueki. 2017;58:1931-1940 pubmed publisher
    ..Mutations of the thrombopoietin receptor MPL and chaperone protein calreticulin gene also induce aberrant activation of JAK and downstream ..
  58. Rostamian M, Niknam H. Evaluation of the adjuvant effect of agonists of toll-like receptor 4 and 7/8 in a vaccine against leishmaniasis in BALB/c mice. Mol Immunol. 2017;91:202-208 pubmed publisher
    ..adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice...
  59. Dong Feng Z, Ting L, Yong Z, Cheng C, Xi Z, Pei Yan K. The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients. Pathol Oncol Res. 2014;20:309-17 pubmed publisher
    ..of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy...
  60. Chou F, Griesinger A, Wunderlich M, Lin S, Link K, Shrestha M, et al. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO. Blood. 2012;120:709-19 pubmed publisher
    ..Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression...
  61. Kato T, Matsumoto A, Ogami K, Tahara T, Morita H, Miyazaki H. Native thrombopoietin: structure and function. Stem Cells. 1998;16:322-8 pubmed
    Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and other organs, circulates in the bloodstream, and is delivered to bone marrow, where it stimulates the early development of multiple hematopoietic lineages ..
  62. Cleyrat C, Darehshouri A, Steinkamp M, Vilaine M, Boassa D, Ellisman M, et al. Mpl traffics to the cell surface through conventional and unconventional routes. Traffic. 2014;15:961-82 pubmed publisher
    ..This study focuses on Mpl trafficking and Jak2 association using two model systems: human erythroleukemia cells (HEL; JAK2V617F) and K562 ..
  63. Koppikar P, Levine R. JAK2 and MPL mutations in myeloproliferative neoplasms. Acta Haematol. 2008;119:218-25 pubmed publisher
    ..Subsequent studies of JAK2V617F-negative MPDs have identified mutations in JAK2 exon 12 and MPL, and these mutations also result in constitutive activation of JAK2 signaling...
  64. Melikyan A, Subortseva I, Sudarikov A, Kovrigina A, Gilyazitdinova E, Kolosheinova T, et al. [Clinical features of essential thrombocythemia and primary myelofibrosis, depending on the molecular characteristics of disease]. Ter Arkh. 2017;89:4-9 pubmed publisher
  65. Defour J, Chachoua I, Pecquet C, Constantinescu S. Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515: implications for myeloproliferative neoplasms. Leukemia. 2016;30:1214-6 pubmed publisher
  66. van den Oudenrijn S, Bruin M, Folman C, Peters M, Faulkner L, de Haas M, et al. Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia. Br J Haematol. 2000;110:441-8 pubmed
    ..The lack of megakaryocyte formation could imply that a defect in the c-mpl gene, encoding the Tpo receptor, exists. Sequencing of c-mpl revealed mutations in four of five patients...
  67. Butcher L, Ahluwalia M, Ord T, Johnston J, Morris R, Kiss Toth E, et al. Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis. Sci Rep. 2017;7:6684 pubmed publisher
    ..In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte antigen expression, as well as ..
  68. Ma W, Zhang X, Wang X, Zhang Z, Yeh C, Uyeji J, et al. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders. Diagn Mol Pathol. 2011;20:34-9 pubmed publisher
    Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs)...
  69. Babaie J, Amiri S, Homayoun R, Azimi E, Mohabati R, Berizi M, et al. Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii. Iran Biomed J. 2018;22:22-32 pubmed
    ..We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii.
  70. Zhang M, Poh T, Louache F, Sundell I, Yuan J, Evans S, et al. Rescue of multi-lineage hematopoiesis during HIV-1 infection by human c-mpl gene transfer and reconstitution of CD34+ progenitor cells in vivo. J Stem Cells. 2009;4:161-77 pubmed
    ..The proto-oncogene c-mpl, identified as the thrombopoietin receptor is involved in multilineage differentiation of CD34+ hematopoietic progenitor cells...
  71. Korde A, Jin L, Zhang J, Ramaswamy A, Hu B, Kolahian S, et al. Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis. Am J Respir Crit Care Med. 2017;: pubmed publisher
    ..Myeloproliferative leukemia oncogene (Mpl) was targeted by miR-1 in the lung endothelium and regulated tumor growth and angiogenesis...
  72. Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, et al. Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat tumbler lock. Sci Signal. 2012;5:ra39 pubmed publisher
    ..Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain. ..
  73. Teichman J, Taher A, Hashi A, Bagai A, Sholzberg M. A sticky situation: myocardial infarction in a young woman with immune thrombocytopenia on eltrombopag and a history of mediastinal radiation. J Thromb Thrombolysis. 2018;45:192-195 pubmed publisher
    More recent immune thrombocytopenia (ITP) treatment strategies enhance platelet production with the use of thrombopoietin receptor agonists (TPO-RA) such as eltrombopag...
  74. Lim K, Chang Y, Chiang Y, Lin H, Chang C, Lin C, et al. Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish. Blood Cancer J. 2016;6:e481 pubmed publisher
    CALR mutations are identified in about 30% of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and primary myelofibrosis...
  75. Chapman J, Geyer J, Khanlari M, Moul A, Casas C, Connor S, et al. Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. Mod Pathol. 2017;: pubmed publisher
    ..had megakaryocytic proliferation and atypia, marrow fibrosis, and myeloproliferative-type driver mutations (JAK2, MPL, CALR)...
  76. Bai J, Shao Z, Shi J, Jia H, Sun J. [Expressions of c-mpl proteins on CD34+ bone marrow cells and platelets of the patients with polycythemia vera]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:1061-4 pubmed
    The objective of this study was to investigate the expressions of TPO receptor (c-mpl) proteins on CD34 positive bone marrow cells (CD34+ BMCs), platelets and the expression of c-mpl mRNA in bone marrow cells of the patients with ..