Combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy requiring novel treatment strategies. The PDE3A inhibitor anagrelide (ANA) profoundly suppresses the proliferation of high PDE3A-expressing AML cells while showing minimal impact on those with low PDE3A expression. Moreover, synergistic effect of ANA with other chemotherapeutic drugs in high PDE3A expression AML cells was observed. The ANA-idarubicin (IDA) combination showed the most remarkable synergistic effect among all ANA-chemotherapeutic drugs commonly used in AML cell line models. Our findings suggest that combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression. mRNA profiles of HEL cells transfected with DMSO, IDA or/and ANA were generated by RNA sequencing using Illumina NovaSeq6000.

急性髓系白血病（Acute myeloid leukemia, AML）是一种侵袭性造血系统恶性肿瘤，亟需开发新型治疗策略。PDE3A抑制剂阿那格雷（anagrelide, ANA）可显著抑制高表达PDE3A的AML细胞增殖，而对低表达PDE3A的AML细胞仅产生极微弱的影响。此外，研究观察到ANA与其他化疗药物联用在高PDE3A表达AML细胞中存在协同效应。在AML细胞系模型中常用的ANA联合化疗药物方案里，ANA与伊达比星（idarubicin, IDA）的联合方案展现出最为显著的协同作用。本研究结果表明，对于高表达PDE3A的AML患者，ANA联合IDA治疗是一种兼具创新性与应用前景的治疗策略。本研究通过Illumina NovaSeq6000平台开展RNA测序，获取了经二甲基亚砜（DMSO）、IDA或联合ANA处理的HEL细胞的mRNA表达谱。