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

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

ABSTRACT

We analyzed the effect of hydroxyurea (HU) on the JAK2V617F allelic ratio (%JAK2V617F), measured in purified blood granulocytes, of patients with polycythemia vera (PV) and essential thrombocythemia (ET). Thirty-six patients were examined sequentially prior to and after start of HU therapy (8 PV, 17 ET), or while remaining untreated (2 PV, 9 ET). HU therapy (median duration: 15 months) reduced the %JAK2V617F by >30% in 13/25 patients (4 PV, 9 ET). 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 PV, 178 ET) or while receiving HU (36 PV, 98 ET; median length of therapy: 32 months), confirmed reduction of %JAK2V617F in the HU-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 thrombocythaemia, allele-specific real time quantitative PCR.