Megakaryopoiesis and platelet function in polycythemia vera and essential thrombocythemia patients with JAK2 V617F mutation.
Patients with Ph chromosome negative myeloproliferative disease (Ph-MPD) have an increased risk of vascular complications. It remains controversial whether patients with the JAK2 V617F mutation (V617F) exhibit increased risk, while recent growing evidence has shown a critical role for V617F in clonal erythropoiesis in Ph-MPD. We studied 53 patients with Ph-MPD especially in relation to megakaryopoiesis, the thrombotic complications and the presence of V617F. Using novel mutation-specific PCR which is a highly sensitive PCR-based assay for detection of JAK2 mutated allele(s), we identified V617F in 38 Ph-MPD, which include 13 polycythemia vera (PV), 23 essential thrombocythemia (ET) and 2 chronic idiopatic myelofibrosis. The numbers of megakaryocytes were significantly increased in PV and ET patients with V617F, but the platelet counts were slightly lower. Although statistically not significant, the incidence of thrombotic events was higher in the group with V617F compared to in those without the mutation. Agonist-induced in vitro platelet aggregation and platelet adhesion were not affected by the presence of this mutation. Nonetheless, we found a hypercoagulable state in Ph-CMPD with V617F by employing whole blood thromboelastography. It suggests pre-thrombotic tendencies in CMPD are complex and JAK2 V617F mutation might have a role in vivo blood coagulation by altering not only the number, but function(s) of all three myeloid cells, including red blood cells, white blood cells and platelets in Ph-CMPD.
Hattori
Norimichi
N
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan. nhattor@med.showa-u.ac.jp.|Department of Clinical Pathology, Showa University, School of Medicine, Shinagawa, Tokyo, Japan. nhattor@med.showa-u.ac.jp.
Fukuchi
Kunihiko
K
Department of Clinical Pathology, Showa University, School of Medicine, Shinagawa, Tokyo, Japan.
Nakashima
Hidetoshi
H
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.|Department of Clinical Pathology, Showa University, School of Medicine, Shinagawa, Tokyo, Japan.
Maeda
Takashi
T
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Adachi
Daisuke
D
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Saito
Bungo
B
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Yanagisawa
Kouji
K
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Matsuda
Isao
I
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Nakamaki
Tsuyoshi
T
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
Gomi
Kunihide
K
Department of Clinical Pathology, Showa University, School of Medicine, Shinagawa, Tokyo, Japan.
Tomoyasu
Shigeru
S
Department of Hematology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000502:physiology*; D001854:Bone Marrow Cells / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D010677:Philadelphia Chromosome; D017354:Point Mutation; D011087:Polycythemia Vera / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D013916:Thrombelastography; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000235:genetics / Q000473:pathology
C507924:JAK2 protein, human; D053614:Janus Kinase 2