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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1377-1380.
Prepublished online as a Blood First Edition Paper on May 4, 2006; DOI 10.1182/blood-2005-11-009605.
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NEOPLASIA
Brief report
Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders
Robert Kralovics,
Soon-Siong Teo,
Sai Li,
Alexandre Theocharides,
Andreas S. Buser,
Andre Tichelli, and
Radek C. Skoda
From the Department of Research, Experimental Hematology, the Division of Clinical Hematology, and the Division of Diagnostic Hematology, Basel University Hospital, Switzerland.
An acquired gain-of-function mutation in the Janus kinase 2 (JAK2-V617F) is frequently found in patients with myeloproliferative disorders (MPDs). To test the hypothesis that JAK2-V617F is the disease-initiating mutation, we examined whether all cells of clonal origin carry the JAK2-V617F mutation. Using allele-specific polymerase chain reaction (PCR) assays for the JAK2 mutation and for the X-chromosomal clonality markers IDS and MPP1, we found that the percentage of granulocytes and platelets with JAK2-V617F was often markedly lower than the percentage of clonal granulocytes determined by IDS or MPP1 clonality assays in female patients. Using deletions of chromosome 20q (del20q) as an autosomal, X-chromosome–independent clonality marker, we found a similar discrepancy between the percentage of cells carrying JAK2-V617F and del20q. Our results suggest that in a proportion of patients with MPDs, JAK2-V617F occurs on the background of clonal hematopoiesis caused by a somatic mutation in an as-yet-unknown gene.
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