Genetic alterations of aggressive NK cell leukemia and identification of molecular target candidates

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Shinshu University
• Principal Investigator: ISHIDA FUMIHIRO 信州大学, 学術研究院保健学系, 教授 (80311695)
• Co-Investigator(Renkei-kenkyūsha): SEKIGUCHI Nodoka 信州大学, 学術研究院医学系(医学部附属病院), 講師 (80720953)
• Research Collaborator: OHSHIMA Koichi 久留米大学, 医学部, 教授 (50203766) ; SUZUMIYA Junji 島根大学, 医学部, 教授 (70206556) ; MUSTJOKI Satu ヘルシンキ大学, 血液学研究ユニット, 教授 ; KIM Wong Seog ソンギョングァン大学, 医学部, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: JAK-STAT系 / NK細胞腫瘍

Outline of Final Research Achievements

Aggressive NK cell leukemia (ANKL) is a malignant hematological disease with poor prognosis which is rare but rather common in young Eastern Asian populations. Diagnostic and therapeutic strategies for ANKL have not been well defined. To elucidate pathogenesis of ANKL and develop novel molecular targets for ANKL, we performed whole-exome sequence analyses of ANKL cells from patients with ANKL. Genetic alterations of several signaling pathways including JAK-STAT and RAS-MAPK, as well as DDX3X and epigenetic modifiers, were identified. Cell lines derived from NK cell malignancies were sensitive to JAK inhibitors, which further demonstrated the importance of JAK-STAT system in the pathogenesis of ANKL. These results provide further insights into molecular pathogenesis of ANKL and target candidates for therapies of NK cell malignancies.

Free Research Field

血液内科学