Functional analysis of STAP, a signal-regulating molecule, in clonal expansion of myeloproliferative tumor stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16243
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Toda Jun 大阪大学, 大学院医学系研究科, 招へい教員 (90770834)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: STAP / MPN

Outline of Final Research Achievements

To investigate whether STAP family molecules are essential for the maintenance of leukemia stem cells other than those in CML, and to establish a therapeutic foundation targeting MPN stem cells, we conducted studies using MPN model mice. Initially, we transplanted bone marrow from JAK2V617F knock-in mice into WT mice and confirmed the MPN phenotype. Subsequently, bone marrow cells from WT, JAK2TG, and JAK2TG/STAP2KO mice were transplanted into irradiated recipient mice. The STAP2KO mice exhibited a higher white blood cell count, more severe anemia, and thrombocytopenia compared to the JAK2TG mice, along with an increase in LK cells. These findings suggest that STAP-2 deficiency may promote the progression of MPN. In contrast, in similar experiments with STAP1KO mice, no significant differences were observed in peripheral blood, bone marrow, or spleen cells. This indicates that while STAP-1 plays a functional role in stem cells in CML, it does not significantly affect MPN stem cells.

Free Research Field

Hematology

Academic Significance and Societal Importance of the Research Achievements

本研究は、白血病幹細胞の維持に必要なSTAPファミリー分子の役割を明らかにし、特にSTAP-2がMPNの進行に寄与する可能性を示しました。この発見は、MPN治療の新たなターゲットを提供し、より効果的な治療法の開発に繋がります。社会的には、白血病患者の生活の質向上と治療成績の向上に寄与し、医療費の削減にも貢献する可能性があります。研究成果は、白血病治療の新たな方向性を示し、将来の臨床応用に大きな期待を寄せています。