Editorial Note: Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1) is one subtype among AML with recurrent genetic abnormalities, characterized by the translocation between chromosome 8q22 and chromosome 21q22. This translocation leads to the fusion of the RUNX1 gene on 8q22 with the RUNX1T1 gene on 21q22, forming the RUNX1-RUNX1T1 fusion gene. From April 14th to 17th, 2024, the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) was held in Glasgow, UK. The conference focused on the latest advancements in stem cell transplantation and cell therapy, advancing towards better clinical outcomes for patients with hematologic diseases and blood tumors. In this congress, the team led by Yi Luo/Yibo Wu from The First Affiliated Hospital of Zhejiang University School of Medicine in China presented a clinical study, sharing the treatment status and prognosis of AML with t(8;21)(q22;q22.1). This journal is honored to invite Dr. Yibo Wu to share the research findings and their clinical significance with colleagues.
“Oncology Frontier – Hematology Frontier”:AML is a highly heterogeneous clonal disease caused by mutations in primitive hematopoietic stem cells. AML with t(8;21) chromosome translocation is listed as one of the common types of AML with recurrent genetic abnormalities. Could you please discuss the current treatment status and prognosis for this type of AML?
Dr. Yibo Wu: AML with t(8;21) chromosome translocation is a subtype of AML with specific genetic features, characterized by the fusion of RUNX1 and RUNX1T1 genes, forming the RUNX1-RUNX1T1 fusion gene. Chromosomal translocation with dual hits represents a process of malignant tumor cell evolution toward the myeloid lineage. Although it is classified as low-risk AML, there is significant heterogeneity clinically. This type of AML accounts for 4% to 8% of all myeloid leukemias, with 30% to 45% of patients experiencing relapse after complete remission. Even with allogeneic hematopoietic stem cell transplantation, some patients still experience relapse. The reasons for the relapse and clinical heterogeneity of this low-risk leukemia are not yet clear.
“Oncology Frontier – Hematology Frontier“: In recent years, there has been increasing attention to the impact of AML heterogeneity on its prognosis and treatment outcomes. Your team conducted research on the heterogeneity of AML disease. Could you please share and interpret the results of this study?
Dr. Yibo Wu: With the development of technologies such as single-cell sequencing, our understanding of tumor diseases, especially AML, has gradually deepened. We now recognize that AML is a multiclonal disease, with each clone having different differentiation states. Different forms of gene mutations directly affect the differentiation status of leukemia cells, which in turn affects the prognosis and outcomes of treatment. Through our research, we found that in AML with t(8;21) chromosome translocation, different differentiation states and gene mutations directly impact prognosis. Particularly, patients with AML of monocytic origin and KIT mutations have the worst prognosis, indicating a high risk of relapse, even after undergoing allogeneic hematopoietic stem cell transplantation.
“Oncology Frontier – Hematology Frontier”: Could you discuss the impact of immunophenotypic classification on the clinical outcomes, survival, and relapse of AML patients?
Dr. Yibo Wu: In the past, our classification of AML was based on traditional FAB morphological classification schemes. With technological advancements, we can now use flow cytometry for immunophenotypic marking and identify cellular differentiation states at the single-cell transcriptome level. For t(8;21) chromosome translocation AML with different differentiation states, concomitant KIT or FLT3 mutations, we can classify them as high-risk AML. Even after undergoing allogeneic hematopoietic stem cell transplantation, this type of AML still carries a high risk of relapse. Therefore, we can employ various measures, including enhancing graft-versus-leukemia effects and upregulating tumor cell antigenicity, to reduce the risk of relapse and improve survival rates. However, due to the high risk of relapse and poor prognosis, more research is needed to explore or elucidate this type of AML further.
“Oncology Frontier – Hematology Frontier”: Could you discuss the significance of this study for future clinical practice?
Dr. Yibo Wu: For the diagnosis of t(8;21) chromosome translocation, we can now perform new risk stratification assessments at the initial diagnosis, distinguishing these high-risk relapse patients from the current European LeukemiaNet (ELN) 2022 AML diagnostic and treatment guidelines. By taking additional measures to reduce relapse and improve survival, we aim to improve the prognosis for these specific patients.
Expert Profile
Professor Yi Luo
Doctor of Medicine, Chief Physician, PhD Supervisor
Associate Director, Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine
High-level Innovative Talent in Health of Zhejiang Province
Deputy Leader, Hematopoietic Stem Cell Transplantation Group, Chinese Society of Hematology, Chinese Medical Association
Standing Committee Member, Hematology Society of Zhejiang Medical Association
Member, Hematologic Oncology Professional Committee, Zhejiang Anti-Cancer Association
Member, Hematopoietic Stem Cell and Cell Therapy Group, Hematologic Oncology Professional Committee, Chinese Anti-Cancer Association
Member, Transplant Infection Academic Committee, Hematology Society, Chinese Society of Geriatrics
Deputy Director, Youth Committee, Hematologic Oncology Professional Committee, Chinese Anti-Cancer Association
Engaged in clinical and basic research on hematopoietic stem cell transplantation for a long time, leading multiple projects funded by the National Natural Science Foundation. Published multiple SCI papers as first or corresponding author in journals such as “Blood,” “Leukemia,” “AJH,” “BJH,” “BMT,” “BBMT,” etc. Received the Second Prize of National Science and Technology Progress Award in 2015, the First Prize of Ministry of Education Science and Technology Progress Award in 2013, and the First Prize of Zhejiang Province Science and Technology Progress Award in 2011.
Expert Profile
Dr. Yibo Wu
PhD, Physician
Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine
Research Interests: Chronic graft-versus-host disease; Clinical and basic research on hematopoietic stem cell transplantation.
As the first author, published 6 papers in prestigious hematology journals such as British Journal of Haematology, Transplantation, and Cellular and Therapy. Participated in the publication of over 12 SCI papers. Serves as a reviewer for journals including Bone Marrow Transplantation. His work has been incorporated into domestic and international clinical guidelines. Principal Investigator for 1 project funded by the National Natural Science Foundation, and participated in 3 National Natural Science Foundation projects. Involved in the formulation and implementation of multiple prospective clinical studies.
