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MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.
MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.
- Source :
-
Blood [Blood] 2008 Jul 01; Vol. 112 (1), pp. 141-9. Date of Electronic Publication: 2008 May 01. - Publication Year :
- 2008
-
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.
- Subjects :
- Adult
Aged
Alleles
Base Sequence
Cohort Studies
DNA, Complementary genetics
Exons
Female
Humans
Janus Kinase 2 genetics
Male
Middle Aged
Myeloproliferative Disorders blood
Polycythemia Vera blood
Polycythemia Vera genetics
Primary Myelofibrosis blood
Primary Myelofibrosis genetics
Prognosis
Prospective Studies
Retrospective Studies
Thrombocythemia, Essential blood
Thrombocythemia, Essential genetics
Mutation
Myeloproliferative Disorders genetics
Receptors, Thrombopoietin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 112
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18451306
- Full Text :
- https://doi.org/10.1182/blood-2008-01-131664