Identification of the cell of origin of infant leukemia with pluripotency

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19540
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Goyama Susumu 東京大学, 大学院新領域創成科学研究科, 教授 (80431849)
• Co-Investigator(Kenkyū-buntansha): 高木 正稔 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (10406267)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 乳児白血病 / リンパ性白血病 / MLL-AF4 / 臍帯血 / シングルセルRNA-seq

Outline of Final Research Achievements

B-cell acute lymphoblastic leukemia with MLL-AF4 translocation is the most common childhood cancer. There are two types, HOXA9 type with high expression of HOXA9 and IRX1 type with high expression of IRX1; HOXA9 type is common in older children and adults, while IRX1 type is found only in infants. In this study, we transduced MLL-AF4 into human cord blood CD34+ cells and transplanted them into immunodeficient NSG mice to generate MLL-AF4 leukemia models with high expression of IRX1 or HOXA9. We also performed single-cell RNA-seq and found that the expression of stem cell-related genes was upregulated in the IRX1 type. These results provide a basis for the development of therapeutic strategies for MLL-AF4 translocated infant leukemia.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

生後1年未満の乳児に発症する白血病を乳児白血病と言います。乳児白血病の多くでMLL遺伝子の異常が認められ、特に、MLL-AF4転座型乳児白血病は、頻度が高くかつ予後も悪いことから臨床上の大きな問題になっています。MLL-AF4転座型白血病は、HOXA9の発現が高いHOXA9型と、IRX1の発現が高いIRX1型の２タイプに分けられます。本研究では、ヒト臍帯血由来の造血幹細胞にMLL-AF4を導入してHOXA9型、IRX1型の２種類の乳児白血病モデルを作製し、さらに単一細胞RNAシークエンシングを行って両者の病態を明らかにしました。これは、乳児白血病に対する治療法開発の基盤となる成果です。