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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.

Authors :
Beer PA
Campbell PJ
Scott LM
Bench AJ
Erber WN
Bareford D
Wilkins BS
Reilly JT
Hasselbalch HC
Bowman R
Wheatley K
Buck G
Harrison CN
Green AR
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.

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