Published online 25 August 2008
Haematologica, Vol 93, Issue 11, 1723-1727 doi:10.3324/haematol.13081
Copyright © 2008 by Ferrata Storti Foundation

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Brief Reports

Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy

François Girodon^1,2, Céline Schaeffer¹, Cédric Cleyrat³, Morgane Mounier², Ingrid Lafont⁴, Frédéric Dos Santos¹, Aurélie Vidal¹, Marc Maynadié¹, Sylvie Hermouet^3,5

¹ Laboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) de Dijon, Dijon
² Registre des hémopathies malignes de Côte d’Or, EA Université de Bourgogne, Dijon
³ INSERM U892, Centre de Recherche en Cancérologie Nantes/Angers, Nantes
⁴ Service d’Hématologie Clinique, CHU de Dijon, Dijon and
⁵ Laboratoire d’Hématologie, Centre Hopitalier Universitaire, Nantes, France

Correspondence: François Girodon, Laboratoire d’Hématologie, Hôpital du Bocage, CHU de Dijon, Dijon, France. E-mail:francois.girodon{at}chu-dijon

ABSTRACT

We analyzed the effect of hydroxyurea on the JAK2V617F allelic ratio (%JAK2V617F), measured in purified blood granulocytes, of patients with polycythemia vera and essential thrombocythemia. Thirty-six patients were examined sequentially prior to and after start of hydroxy-urea therapy (8 polycythemia vera, 17 essential thrombocythemia), or while remaining untreated (2 polycythemia vera, 9 essential thrombocythemia). Hydroxyurea therapy (median duration: 15 months) reduced the %JAK2V617F by >30% in 13/25 patients (4 polycythemia vera, 9 essential thrombocythemia). For 3 patients, JAK2V617F remained undetectable for 3–27 months. In addition, a single time point study of two large cohorts of patients, examined either at the time of diagnosis (99 polycythemia vera, 178 essential thrombocythemia) or while receiving hydroxyurea (36 polycythemia vera, 98 essential thrombocythemia; median length of therapy: 32 months), confirmed reduction of %JAK2V617F in the hydroxyurea-treated group (24% vs. 33% JAK2V617F at diagnosis, p<0.01). Prospective studies are needed to determine the prognostic value of reduced JAK2V617F allele burden under cytoreductive therapy.

Key words: JAK2V617F, hydroxyurea, myeloproliferative neoplasm, polycythemia vera, essential thrombocythemia, allele-specific real time quantitative PCR.

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