Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy.
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.
Girodon
François
F
Laboratoire d'Hématologie, Hôpital du Bocage, CHU de Dijon, Dijon, France. francois.girodon@chu-dijon
Schaeffer
Céline
C
Cleyrat
Cédric
C
Mounier
Morgane
M
Lafont
Ingrid
I
Santos
Frédéric Dos
FD
Duval
Aurélie
A
Vidal
Aurélie
A
Maynadié
Marc
M
Hermouet
Sylvie
S
D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000986:Antisickling Agents / Q000627:therapeutic use; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics
D000986:Antisickling Agents; D017931:DNA Primers; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea