Exploring novel JAK2 mutations for definitive diagnostics of polycythemia vera

• Project/Area Number: 25860416
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Juntendo University
• Principal Investigator: Morishita Soji 順天堂大学, 医学部, 助教 (10635866)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 真性赤血球増加症 / 骨髄増殖性腫瘍 / JAK2遺伝子 / 次世代シークエンス / 遺伝子変異検出 / JAK2V617F変異検出

Outline of Final Research Achievements

Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by a clonal expansion of the hematopoietic/progenitor stem cells and an overproduction of blood cells, and mainly consists of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2 mutation positivity in these diseases was 94.4% in PV, 51.9% in ET, and 54.7% in PMF. In the mutant JAK2 negative PV cohort, 2 recurrent SNPs were identified using next generation sequencing based technique targeting whole JAK2 exons. These SNPs are specifically identified in Asians; however, both of the two are silent-mutations. For the diagnostic of PV, detecting the positivity of JAK2 mutations should be considered.

Research Products

• [Journal Article] Melting curve analysis after T allele enrichment (MelcaTle) as a highly sensitive and reliable method for detecting the JAK2V617F mutation. (2015)
  • Author(s): Morishita S, Takahashi K, Araki M, Hironaka Y, Sunami Y, Edahiro Y, Tsutsui M, Ohsaka A, Tsuneda S, Komatsu N.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: e0122003-e0122003
  • DOI: 10.1371/journal.pone.0122003
  • Peer Reviewed / Open Access
• [Journal Article] JAK2, CALR, and MPL mutation status in Japanese myeloproliferative neoplasms patients (2015)
  • Author(s): Shirane S, Araki M, Morishita S, Edahiro Y, Sunami Y, Hironaka Y, Noguchi M, Koike M, Ohsaka A, and Komatsu N
  • Journal Title: Haematologica Volume: 100 Issue: 2 Pages: e46-e48
  • DOI: 10.3324/haematol.2014.115113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay (2014)
  • Author(s): Takei H, Morishita S, Araki M, Edahiro Y, Sunami Y, Hironaka Y, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, and Komatsu N
  • Journal Title: PLoS ONE Volume: 9 Issue: 8 Pages: e104958-e104958
  • DOI: 10.1371/journal.pone.0104958
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan (2014)
  • Author(s): EdahiroY, Morishita S, Takahashi K, Hironaka Y, Yahata Y, Sunami Y, Shirane S, Tsutsui M, Noguchi M, Koike M, Imai K, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, Araki M, Komatsu N
  • Journal Title: Int J Hematol Volume: 99(5) Issue: 5 Pages: 625-634
  • DOI: 10.1007/s12185-014-1567-1
  • Peer Reviewed
• [Presentation] Activation of AP-1 by JAK2V617F through induction and stabilization of c-FOS (2015)
  • Author(s): Edahiro Y, Araki M, Hironaka Y, Yang I, Morishita S, Sunami Y, Ohsaka A, and Komatsu N
  • Organizer: The 57th ASH Annual Meeting
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Early disease onset of patients with triple-negative myeloproliferative neoplasms (2015)
  • Author(s): 白根脩一，荒木真理人，森下総司，枝廣陽子，竹井拓，津村真知子，弘中由美，落合友則，三澤恭平，大坂顯通，小松則夫
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-10-16
• [Presentation] A highly specific method for detecting a single copy JAK2V617F mutation (2015)
  • Author(s): 森下総司，荒木真理人，弘中由美，角南義孝，枝廣陽子，筒井深雪，大坂顯通，小松則夫
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-10-16
• [Presentation] Establishment of iPS cells from myeloproliferative neoplasms patients with CALR mutation (2015)
  • Author(s): 竹井拓，森下総司，荒木真理人，水上喜久，枝廣陽子，角南義孝，弘中由美，津村真知子，常田聡，遠藤大，中村壮，江藤浩之，大坂顯通，小松則夫
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-10-16
• [Presentation] A interim analysis of stop trial against CMP-CP in CMR patients who had received sequential TKIs (2015)
  • Author(s): 佐藤恵理子，森下総司，野口雅章，小池道明，大津洋，小松則夫
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-10-16
• [Presentation] Melting curve analysis after T allele enrichment: a highly sensitive and reliable method for detecting the JAK2V617F mutation (2015)
  • Author(s): Morishita S, Takahashi K, Araki M, Hironaka Y, Sunami Y, Edahiro Y, Tsutsui M, Ohsaka A, Tsuneda S, and Komatsu N
  • Organizer: The 6th JSH International Symposium
  • Place of Presentation: Nagano, Japan
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] Dynamic increase in JAK2V617F allele burden is a predictive parameter for the transformation into myelofibrosis from polycythemia vera and essential thrombocythosis (2014)
  • Author(s): Shirane S, Araki M, Morishita S, Hironaka Y, Noguchi M, Koike M, Hirano T, Ohsaka A, and Komatsu N
  • Organizer: The 56th ASH Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Establishment of a novel assay for MPLW515/K detection and allele burden measurement (2014)
  • Author(s): 竹井拓，森下総司，荒木真理人，枝廣陽子，角南義孝，弘中由美，野田尚宏，関口勇地，常田聡，大坂顯通，小松則夫
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] MPL mutation analysis of Ph-negative myeloproliferative neoplasms in Japan (2014)
  • Author(s): 枝廣陽子，白根脩一，竹井拓，森下総司，角南義孝，弘中由美，常田聡，大坂顯通，荒木真理人，小松則夫
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] An epidemiologic study of classical Ph-negative myeloproliferative neoplasms (MPNs) in Japan (2013)
  • Author(s): Yoko Edahiro, Soji Morishita, Kochi Takahashi, Yoshitaka Sunami, Yuriko Yahata, Marito Araki, Satoshi Tsuneda, Akimichi Ohsaka, and Norio Komatsu
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Patent(Industrial Property Rights)] 遺伝子変異の検出方法及びそれに用いる蛍光標識オリゴヌクレオチド (2015)
  • Inventor(s): 山口 正裕，蔵田 信也，小松 則夫，森下 総司
  • Industrial Property Rights Holder: 山口 正裕，蔵田 信也，小松 則夫，森下 総司
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-03-31
  • Acquisition Date: 2015-10-02