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Mutations in the juxtamembrane region of the thrombopoietin receptor MPL (Myeloproliferative leukemia virus oncogene homology) have been described in JAK2 V617F-negative PMF and ET [Pickman Y et al. PLoS Medicine. 2006, Pardanani A et al. Blood. 2006].
MPL belongs to the hematopoietin superfamily and in vitro studies have shown that expression of MPL W515L constitutively activates JAK2 and downstream signaling pathways. However, the clinical phenotype is distinct, with marked thrombocytosis and myelofibrosis...
The gene maps to chromosome 1p34 and contains 12 exons. The mutation is located within exon 10 and leads to a G to T transition at nucleotide 1544 resulting in a tryptophan to leucine substitution at codon 515 of the transmembrane region. Subsequently, a MPL W515K (TG 1543/4 to AA) was identified [Chaligné R et al. Blood. 2007, Vannucchi A et al. Haematologica. 2008]. MPL W515L and MPL W515K gain-of-function mutations were both detected in about 10% and 3% of PMF and ET respectively, but never in PV. Since then, additional MPL mutations have been reported within exon 10 [Savoia A et al. Haematologica. 2007].Consequently, detecting MPL 515 mutations in JAK2 V617F-negative sample can facilitate MPN diagnostics [Tefferi A et al. Leukemia 2008].
IPSOGEN MPL515 L/K MutaScreen™ Kit uses PCR amplification of genomic DNA for sensitive and reproducible detection of the MPL515 L and K mutations.
Allelic discrimination for qualitative detection on genomic DNA
Single tube reaction for MPL515 mutation and wild type detection (for each mutation independently)
Cut-off for Positivity at 1.5% for each mutation
Product manufactured under ISO 13485 certification ensuring optimal quality control and full traceability
Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms.
Leukemia. 2008
Authors: Tefferi A et al.
MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
PLoS Medicine. 2006
Authors: Pikman Y et al.
MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
Blood. 2006
Authors: Pardanani AD et al.
Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis
Blood. 2007
Authors: Chaligné R et al.
Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations
Haematologica. 2008
Authors: Vannucchi AM and Guglielmelli P
Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations
Haematologica. 2007
Authors: Savoia A et al.
