MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort
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Open Access
- 1 July 2008
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 112 (1), 141-149
- https://doi.org/10.1182/blood-2008-01-131664
Abstract
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. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F− patients and a single V617F+ patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F+ ET patients, those with MPL mutations displayed lower hemoglobin and higher platelet levels at diagnosis, higher serum erythropoietin levels, endogenous megakaryocytic but not erythroid colony growth, and reduced bone marrow erythroid and overall cellularity. Compared with V617F− patients, those with MPL mutations were older with reduced bone marrow cellularity but could not be identified as a discrete clinicopathologic subgroup. MPL mutations lacked prognostic significance with respect to thrombosis, major hemorrhage, myelofibrotic transformation or survival.Keywords
This publication has 42 references indexed in Scilit:
- Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disordersBlood, 2008
- Prevalance of JAK2 V617F and exon 12 mutations in polycythaemia veraBritish Journal of Haematology, 2007
- Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemiaBlood, 2007
- JAK2Exon 12 Mutations in Polycythemia Vera and Idiopathic ErythrocytosisNew England Journal of Medicine, 2007
- Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective studyThe Lancet, 2005
- A Gain-of-Function Mutation ofJAK2in Myeloproliferative DisordersNew England Journal of Medicine, 2005
- Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosisCancer Cell, 2005
- A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia veraNature, 2005
- Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disordersThe Lancet, 2005
- Polycythemia Vera: Stem-Cell and Probable Clonal Origin of the DiseaseNew England Journal of Medicine, 1976