Investigation of molecular biology of CNS leukemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03653
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kato Motohiro 東京大学, 医学部附属病院, 教授 (40708690)
• Co-Investigator(Kenkyū-buntansha): 内山 徹 国立研究開発法人国立成育医療研究センター, 成育遺伝研究部, 室長 (10436107) ; 加藤 格 京都大学, 医学研究科, 助教 (10610454)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌 / 白血病

Outline of Final Research Achievements

In this study, whole exome sequencing was performed in 11 patients with extramedullary relapsed ALL to elucidate the molecular mechanisms of treatment resistance leading to extramedullary recurrence. The genomic profile at relapse differed from that at initial disease, suggesting that minor clones at diagnosis contributed to the recurrence. In addition, 5 of the 11 were found to have abnormalities in gene X, and high relapse rate of patients with this alteration was reproduced in the validation cohort. The results confirm that suppression of gene X function results in rapid DNA repair and may favor survival of leukemic cells against chemotherapy-induced DNA damage.

Free Research Field

小児科学、分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

急性リンパ性白血病の治療成績は向上し、免疫療法薬剤などの開発により骨髄再発のコントロールは可能になった。一方で、依然として中枢神経再発に対する治療開発は限られており、頭蓋照射などは晩期合併症の高リスクとなる。本研究の成果により、中枢神経再発の機序が明らかになり、再発リスクの特定だけでなく、中枢神経再発の機序を直接の標的とした治療開発につながることが期待される。