It has long been recognized that allogeneic hematopoietic stem cell transplantation can reduce the risk of leukemia relapse by inducing the graft-versus-leukemia effect. However, allogeneic stem cell transplantation is also known to be able to cause graft-versus-host disease, which can cause considerable morbidity and even mortality in patients receiving allogeneic hematopoietic stem cell transplantation. Therefore, to elicit leukemia-specific immune responses without alloimmune reaction, the possibilities of active immunotherapy methods such as leukemia vaccines have been studied for decades. Among various types of leukemia vaccines, whole leukemia cell vaccines are known to be able to induce immune responses against multiple unknown antigens without the need for adoptive transfer of dendritic cells. In this review, we will discuss the past progress of whole leukemia cell vaccines, with a focus on strategies to enhance their immunogenicity. We will also present the future directions of whole leukemia cell vaccines along with addressing newly emerging concepts, such as immunogenic cell death and necroptosis. We will not discuss in detail other factors that can reduce the therapeutic efficacy of whole leukemia cell vaccines such as various immunosuppressive mechanisms of leukemia.

Inki Moon, M.D., M.S., Min Gyu Kong, M.D., M.S., Young Sok Ji, M.D., M.S., Se Hyung Kim, M.D., Ph.D., Seong Kyu Park, M.D., Ph.D., Jon Suh, M.D., Ph.D., and Mi-Ae Jang, M.D., Ph.D.. Ann Lab Med 2023;43:145-52. https://doi.org/10.3343/alm.2023.43.2.145

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

Ji YS, et al. Yonsei Med J. 2023 Jan;64:e14. https://doi.org/10.3349/ymj.2022.0331

Kim SH, et al. J Korean Med Sci. 2023 Aug;38(36):e281. https://doi.org/10.3346/jkms.2023.38.e281