Hematopoietic clonal dominance, stem cell mutations, and evolutionary pattern of JAK2V617F allele burden in polycythemia vera. (13th September 2014)

• Record Type: Journal Article
• Authors: Angona, Anna; Alvarez‐Larrán, Alberto; Bellosillo, Beatriz; Martínez‐Avilés, Luz; Camacho, Laura; Fernández‐Rodríguez, Concepción; Pairet, Silvia; Longarón, Raquel; Ancochea, Águeda; Senín, Alicia; Florensa, Lourdes; Besses, Carles
• Is Part Of: European journal of haematology. Volume 94:Number 3(2015:Mar.)
• Page Start: 251
• Page End: 257
• Publication Date: 2014-09-13
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12425
• Languages: English
• ISSNs: 0902-4441

Abstract

<abstract abstract-type="main" id="ejh12425-abs-0001"> <title>Abstract</title> <sec id="ejh12425-sec-0001" sec-type="section"> <title>Objectives</title> <p>Clonal dominance is characteristic of patients with post‐polycythemia vera myelofibrosis (post‐PV MF), whereas patients in chronic phase usually display polyclonal hematopoiesis. The aim of this work was to study the mutational burden of <italic>JAK2</italic>V617F at the progenitor level in patients with PV and correlate it with the evolutive phase of the disease and the presence of mutations in genes different to <italic>JAK2</italic>V617F.</p> </sec> <sec id="ejh12425-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>JAK2</italic>V617F was measured in stem cells, progenitor cells, and granulocytes of 45 patients with PV (early chronic phase <italic>n</italic> = 26, late chronic phase <italic>n</italic> = 10, post‐PV MF <italic>n</italic> = 9). In addition, screening of <italic>TET2</italic>, <italic> DNMT3A</italic>, <italic> ASXL1</italic>, <italic> SF3B1</italic>, <italic> SRSF2</italic>, <italic> U2AF1</italic>, and <italic>TP53</italic> was performed with quantification of the mutation in CD34+ cells in positive cases. Moreover, we assessed whether <italic>JAK2</italic>V617F allele burden in granulocytes (at a single time point or monitoring) could be used as a surrogate of clonal dominance.</p> </sec> <sec id="ejh12425-sec-0003" sec-type="section"> <title>Results</title> <p>Ten patients presented clonal dominance at progenitor level (PV at diagnosis <italic>n</italic> = 2, late chronic phase <italic>n</italic> = 1, post‐PV MF <italic>n</italic> = 7). Additional mutations were identified in four patients at diagnosis, three in <italic>TET2</italic>, and one in <italic>DNMT3A</italic> gene, with clonal dominance present in three of them. At PV diagnosis, clonal dominance was demonstrated only in patients with additional mutations. <italic>JAK2</italic>V617F monitoring showed better diagnostic accuracy than single time point measurement as a marker of clonal dominance.</p> </sec> <sec id="ejh12425-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Clonal dominance may be present at diagnosis, especially in those cases carrying other mutations. <italic>JAK2</italic>V617F monitoring during follow‐up could help in the identification of patients with clonal dominance.</p> </sec> </abstract>