Mutated genes in cancer (59) – MPL

MPL

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 4352 or MPL

● Ensembl (http://www.ensembl.org/index.html): ENSG00000117400

● UniProt (http://www.uniprot.org/): P40238

● OMIM (http://www.ncbi.nlm.nih.gov/omim): 159530

● GeneCards (http://www.genecards.org/): MPL

● HGNC (http://www.genenames.org/): 7217 or MPL

Gene locus:

1p34

Protein name:

Myeloproliferative leukemia virus oncogene

Protein Size:

635 amino acids; about 71 kDa

Function:

The protein encoded by MPL is a receptor for thrombopoietin (TPO-R). Thrombopoietin is the major regulator of megakaryocytopoiesis and platelet formation. Upon binding of thrombopoietin TPO-R is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.

Cancer-related alterations:

Somatic MPL mutations (essentially missense substitutions) have been found exclusively in haematopoietic and lymphoid tissue tumors. These mutations are observed in a region corresponding to aminoacids 505-519, with a hot spot at aminoacid 515

References (open access):

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Tefferi A. Leukemia. 2010 Jun;24(6):1128-38.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035972/pdf/leu201069a.pdf

Advances in understanding and management of myeloproliferative neoplasms. Vannucchi AM, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009 May-Jun;59(3):171-91

http://onlinelibrary.wiley.com/doi/10.3322/caac.20009/pdf

Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms. Beer PA, Ortmann CA, Stegelmann F, Guglielmelli P, Reilly JT, Larsen TS, Hasselbalch HC, Vannucchi AM, Möller P, Döhner K, Green AR. Haematologica. 2010 Dec;95(12):2153-6.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995575/pdf/0952153.pdf