CLEC12A 在急性髓系白血病中的预后和治疗作用。

Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia.

机构信息

Department of Hematology, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.

出版信息

Blood Rev. 2019 Mar;34:26-33. doi: 10.1016/j.blre.2018.10.003. Epub 2018 Nov 1.

DOI:10.1016/j.blre.2018.10.003

PMID:30401586

Abstract

CLEC12A has recently been identified as an antigen, expressed on leukemic stem cells and leukemic blasts. Given the fact that this expression profile seems stable throughout diagnosis, treatment and relapse on leukemic blasts and leukemic stem cells, CLEC12A can be considered a highly potent and reliable marker for the detection of measurable residual disease and therefore applicable for risk stratification and prognostication in AML. Low CLEC12A expression on leukemic blasts seems to be independently associated with lower likelihood of achieving complete remission after 1 cycle of induction chemotherapy, shorter event free survival, as well as overall survival, indicating potential prognostic properties of CLEC12A expression itself. Lack of expression on the normal hematopoietic stem and progenitor cells, in contrast to CD123 and CD33, might result in less toxicity regarding cytopenias, making CLEC12A an interesting target for innovating immunotherapies, including monoclonal and bispecific antibodies, antibody-drug conjugates and CAR-T cells therapy.

摘要

CLEC12A 最近被鉴定为一种抗原，在白血病干细胞和白血病原始细胞上表达。鉴于这种表达谱在白血病原始细胞和白血病干细胞的诊断、治疗和复发过程中似乎很稳定，CLEC12A 可以被认为是检测可测量残留疾病的高度有效和可靠的标志物，因此可用于 AML 的风险分层和预后判断。白血病原始细胞上的低 CLEC12A 表达似乎与诱导化疗 1 个周期后完全缓解的可能性降低、无事件生存时间以及总生存时间缩短独立相关，表明 CLEC12A 表达本身具有潜在的预后特性。与 CD123 和 CD33 不同，CLEC12A 在正常造血干细胞和祖细胞上缺乏表达，这可能导致细胞减少症的毒性降低，使 CLEC12A 成为创新免疫疗法的一个有趣靶点，包括单克隆和双特异性抗体、抗体药物偶联物和 CAR-T 细胞疗法。