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免疫表型与拓扑异构酶 IIα 和 β 在成人急性髓细胞白血病中表达的相关性。

Association of immunophenotype with expression of topoisomerase II α and β in adult acute myeloid leukemia.

机构信息

Cleveland Clinic, Cleveland, OH, USA.

SWOG Statistical Center, Seattle, WA, USA.

出版信息

Sci Rep. 2020 Mar 26;10(1):5486. doi: 10.1038/s41598-020-62345-9.

DOI:10.1038/s41598-020-62345-9
PMID:32218491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7099013/
Abstract

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIβ (P < 0.0001). In contrast to topo IIα, topo IIβ was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.

摘要

用于治疗急性髓系白血病 (AML) 的蒽环类药物抑制哺乳动物拓扑异构酶 II (topo II) 同工酶，即 topo IIα 和 topo IIβ 的活性。我们通过 RT-PCR 测定了接受一线阿糖胞苷/柔红霉素治疗的 230 例非 M3 AML 患者的 topo IIα 和 topo IIβ 的表达，并研究其与免疫表型 (IP) 和结局的关系。通过逻辑或 Cox 回归分析治疗结局。在 211 例可进行分析的患者中，topo IIα 的表达明显低于 topo IIβ（P<0.0001）。与 topo IIα 相反，topo IIβ 与骨髓或血液中的原始细胞百分比（P=0.0001）、CD7（P=0.01）、CD14（P<0.0001）和 CD54（P<0.0001）显著相关。CD56 阴性患者无事件生存时间明显差于 CD56 高表达患者（HR=1.9，95%CI[1.0-3.5]，p=0.04），CD15 低表达患者总生存时间明显差于 CD15 高表达患者（HR=2.2，95%CI[1.1-4.2]，p=0.02）。Ingenuity 通路分析表明，topo IIβ 和免疫表型标志物在与细胞间信号、造血系统发育/功能和炎症反应相关的网络中存在关联。topo IIβ 的表达反映了高度增殖性疾病和独特 IP 的疾病生物学，但似乎不是影响接受蒽环类药物治疗的成人 AML 患者结局的独立变量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/75ea0ba328a3/41598_2020_62345_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/a019030fdf0e/41598_2020_62345_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/14e9ed5d2387/41598_2020_62345_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/75ea0ba328a3/41598_2020_62345_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/a019030fdf0e/41598_2020_62345_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/14e9ed5d2387/41598_2020_62345_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e627/7099013/75ea0ba328a3/41598_2020_62345_Fig3_HTML.jpg

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