威尼斯人
阿扎胞苷
髓系白血病
医学
低甲基化剂
肿瘤科
内科学
化疗
白血病
临床试验
阿糖胞苷
免疫学
生物信息学
DNA甲基化
基因
生物
遗传学
慢性淋巴细胞白血病
基因表达
作者
Philipp Makowka,Verena Stolp,Karoline Stoschek,Hubert Serve
标识
DOI:10.1515/hsz-2021-0288
摘要
Acute myeloid leukemia (AML) is a heterogeneous, highly malignant disease of the bone marrow. After decades of slow progress, recent years saw a surge of novel agents for its treatment. The most recent advancement is the registration of the Bcl-2 inhibitor ventoclax in combination with a hypomethylating agent (HMA) in the US and Europe for AML patients not eligible for intensive chemotherapy. Treatment of newly diagnosed AML patients with this combination results in remission rates that so far could only be achieved with intensive treatment. However, not all AML patients respond equally well, and some patients relapse early, while other patients experience longer periods of complete remission. A hallmark of AML is its remarkable genetic, molecular and clinical heterogeneity. Here, we review the current knowledge about molecular features of AML that help estimate the probability of response to venetoclax-containing therapies. In contrast to other newly developed AML therapies that target specific recurrent molecular alterations, it seems so far that responses are not specific for a certain subgroup. One exception is spliceosome mutations, where good response has been observed in clinical trials with venetoclax/azacitidine. These mutations are rather associated with a more unfavorable outcome with chemotherapy. In summary, venetoclax in combination with hypomethylating agents represents a significant novel option for AML patients with various molecular aberrations. Mechanisms of primary and secondary resistance seem to overlap with those towards chemotherapy.
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