Lenalidomide as IKZF1 inhibitor induces Ph+ALL cells into apoptosis synergy with antileukemic agents

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19635
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: HARAMA Daisuke 山梨大学, 医学部附属病院, 医員 (10774078)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: フィラデルフィア染色体 / 急性白血病 / 新規治療法 / IKZF1

Outline of Final Research Achievements

Combination use of lenalidomide (LEN) and imatinib (IM) on Philadelphia chromosome positive leukemia cell line showed synergistic antileukemic effect against using IM single agent. In addition, the same effect was further enhanced by using dexamethasone (DEX) in addition of LEN and IM. It was also observed that IKZF1 isoform was degraded in the presence of LEN, without mutated isoform Ik6, leading to be susceptible to TKI. This synergistic effect was also demonstrated in xenograft model using NOG mice. In comparison of mice without treatment, mice receiving LEN and IM longed survival time of approximately 180%.
LEN, IM, and DEX are all internal medicines, indicating the possibility of leading to a treatment that maintains QOL of leukemia patients.

Free Research Field

血液学