t(8;21)(q22;q22);(RUNX1::RUNX1T1) 的急性髓系白血病 (AML) 具有高度异质性和恶性性。它的复发率接近 40%，导致临床对化疗产生耐药性或难治性。免疫细胞，特别是 CD4( ) T 和 CD8( ) T 淋巴细胞，已被发现在这种情况下功能失调，而功能恢复在临床前试验中显示出有希望的效率。在这里，我们利用来自患有 RUNX1::RUNX1T1 的新发 AML 患者以及疾病进展后各个阶段的单细胞转录组数据，研究了与 T 细胞增殖和激活相关的基因。在白血病细胞中，与诊断时的 T 细胞相比，ADA、AHCY、GPN3 和 LTBR 的表达显着高，并且随着疾病进展而增加。此外，我们发现 AHCY 是预测 RUNX1::RUNX1T1 AML 患者总生存期和无复发生存期的有效生物标志物。还研究了 AHCY 与浸润的免疫细胞和免疫检查点的相关性。来自另外两项独立研究 TCGA LAML（n = 145）和 GEO 数据集（n = 104）的 AML 队列也表明，AHCY 高表达的 AML 患者的预后较差。总之，我们的研究表明，AHCY 可能作为预测 RUNX1::RUNX1T1 AML 患者的预后和 T 细胞增殖和激活效率的新指标。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

Acute myeloid leukemia (AML) with t(8;21)(q22;q22);(RUNX1::RUNX1T1) is highly heterogeneous and malignant. It has a relapse rate of nearly 40 %, resulting in clinical resistance or refractoriness to chemotherapy. Immune cells, particularly CD4(+) T and CD8(+) T lymphocytes, have been discovered to be dysfunctional in this condition, and functional recovery shows promising efficiency in preclinical trials. Here, with single-cell transcriptomic data from de novo AML patients with RUNX1::RUNX1T1 and at various stages following disease progression, we investigated the genes correlated with T-cell proliferation and activation. In leukemia cells, ADA, AHCY, GPN3 and LTBR were markedly highly expressed compared to those in T-cell at diagnosis, and they tended to increase with disease progression. Additionally, we discovered that AHCY was an effective biomarker to predict the overall survival as well as relapse-free survival of AML patients with RUNX1::RUNX1T1. The correlation of AHCY with infiltrated immune cells and immune checkpoints was also investigated. AML cohorts from two other independent studies, TCGA LAML (n = 145) and the GEO dataset (n = 104), also demonstrated an inferior outcome for AML patients with high AHCY expression. In conclusion, our research revealed that AHCY might function as a novel indicator to predict the prognosis and efficiency of T-cell proliferation and activation in AML patients with RUNX1::RUNX1T1.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.