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CD123在突变型急性髓系白血病细胞上持续表达。

CD123 Is Consistently Expressed on -Mutated AML Cells.

作者信息

Perriello Vincenzo Maria, Gionfriddo Ilaria, Rossi Roberta, Milano Francesca, Mezzasoma Federica, Marra Andrea, Spinelli Orietta, Rambaldi Alessandro, Annibali Ombretta, Avvisati Giuseppe, Di Raimondo Francesco, Ascani Stefano, Falini Brunangelo, Martelli Maria Paola, Brunetti Lorenzo

机构信息

Department of Medicine and Surgery, University of Perugia, 06131 Perugia, Italy.

Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, 24127 Bergamo, Italy.

出版信息

Cancers (Basel). 2021 Jan 28;13(3):496. doi: 10.3390/cancers13030496.

Abstract

-mutated (mut) acute myeloid leukemia (AML) comprises about 30% of newly diagnosed AML in adults. Despite notable advances in the treatment of this frequent AML subtype, about 50% of mut AML patients treated with conventional treatment die due to disease progression. CD123 has been identified as potential target for immunotherapy in AML, and several anti-CD123 therapeutic approaches have been developed for AML resistant to conventional therapies. As this antigen has been previously reported to be expressed by mut cells, we performed a deep flow cytometry analysis of CD123 expression in a large cohort of mut and wild-type samples, examining the whole blastic population, as well as CD34CD38 leukemic cells. We demonstrate that CD123 is highly expressed on mut cells, with particularly high expression levels showed by CD34CD38 leukemic cells. Additionally, CD123 expression was further enhanced by mutations, which frequently co-occur with mutations. Our results identify -mutated and particularly double-mutated AML as disease subsets that may benefit from anti-CD123 targeted therapies.

摘要

-突变型(mut)急性髓系白血病(AML)约占成人新诊断AML的30%。尽管在这种常见的AML亚型治疗方面取得了显著进展,但接受传统治疗的mut AML患者中约有50%因疾病进展而死亡。CD123已被确定为AML免疫治疗的潜在靶点,并且已经针对对传统疗法耐药的AML开发了几种抗CD123治疗方法。由于此前有报道称该抗原在mut细胞中表达,我们对大量mut和野生型样本中的CD123表达进行了深度流式细胞术分析,检测了整个原始细胞群体以及CD34CD38白血病细胞。我们证明CD123在mut细胞上高度表达,CD34CD38白血病细胞显示出特别高的表达水平。此外,CD123表达因突变而进一步增强,这些突变常与 突变同时发生。我们的结果确定 -突变型尤其是 双突变型AML为可能受益于抗CD123靶向治疗的疾病亚组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d703/7865228/c83230249935/cancers-13-00496-g001.jpg

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