Uncovering malignant mechanisms in multiple myeloma cells using CRISPR/Cas9 system

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19561
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Aichi Medical University
• Principal Investigator: Ota Akinobu 愛知医科大学, 医学部, 講師 (30438048)
• Research Collaborator: SIVASUNDARAM Karnan
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 多発性骨髄腫 / 悪性化 / Interleukin-6 / cDNAマイクロアレイ / CRISPR/Cas9

Outline of Final Research Achievements

Multiple myeloma (MM) is a hematopoietic malignancy with complex and/or different types of genetic background. Although novel therapeutic agents and their combination therapies are more effective than before, MM remains to be an incurable disease. Thus, development of novel molecular-targeted therapies is required to overcome malignant phenotype of MM. Here, the researcher tried to uncover the malignant mechanism of MM using CRISPR/Cas9 system. cDNA microarray analyses revealed that a novel interleukin-6 (IL-6)-inducible serine/threonine kinase X increased after IL-6 treatment in IL-6-dependent MM cell lines, ANBL-6 and FLAM-76. Both mRNA and protein expression of X kinase were detectable and were over-expressed in a subset of MM cell lines. CRISPR/Cas9-mediated gene disruption of gene X resulted in tumor suppression in MM cells. Collectively, these results suggest that novel IL-6-inducible kinase X might be a promising molecular target for MM therapy.

Free Research Field

癌の分子生物学