Potential for subsets of wt-NPM1 primary AML blasts to respond to retinoic acid treatment.
Potential for subsets of wt-NPM1 primary AML blasts to respond to retinoic acid treatment.
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DOI：
10.18632/oncotarget.23642
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Yen A
中科院分区：
文献类型：
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作者：
Bunaciu RP;MacDonald RJ;Gao F;Johnson LM;Varner JD;Wang X;Nataraj S;Guzman ML;Yen A
急性髓性白血病（AML）具有高死亡率，这可能反映了对各种亚型的分子多样性缺乏了解以及缺乏已知的可操作靶点。目前有12个开放的AML临床试验使用联合治疗方式，包括全反式维甲酸（RA）。突变型核磷蛋白-1被提议作为RA反应的可能标志物，是三项活动性RA 3期临床试验招募患者的标准。我们测试了RA单独或与博舒替尼（B）或6-甲酰吲哚并（3，2-B）咔唑（F）联合诱导12例初治AML样本向更分化表型转化的能力。我们评估了与分化、醛脱氢酶活性和葡萄糖摄取活性相关的细胞表面标志物的表达水平。RA和B或F联合处理降低了集落形成能力，并与c-Cbl/林恩/c-Raf中心信号体的调节相关。联合治疗在大多数情况下比单独使用RA更有效。基于他们对治疗的反应，一些原发性白血病样本比其他原发性样本更接近HL-60细胞，这表明它们可能代表迄今为止未定义的AML亚型，其在联合分化治疗中可能对RA有反应。
Acute myeloid leukemia (AML) has high mortality rates, perhaps reflecting a lack of understanding of the molecular diversity in various subtypes and a lack of known actionable targets. There are currently 12 open clinical trials for AML using combination therapeutic modalities including all-trans retinoic acid (RA). Mutant nucleophosmin-1, proposed as a possible marker for RA response, is the criterion for recruiting patients in three active RA phase 3 clinical trials. We tested the ability of RA alone or in combination with either bosutinib (B) or 6-formylindolo(3,2-b) carbazole (F) to induce conversion of 12 de novo AML samples toward a more differentiated phenotype. We assessed levels of expression of cell surface markers associated with differentiation, aldehyde dehydrogenase activity, and glucose uptake activity. Colony formation capacity was reduced with the combined treatment of RA and B or F, and correlated with modulation of a c-Cbl/Lyn/c-Raf-centered signalsome. Combination treatment was in most cases more effective than RA alone. Based on their responses to the treatments, some primary leukemic samples cluster closer to HL-60 cells than to other primary samples, suggesting that they may represent a hitherto undefined AML subtype that is potentially responsive to RA in a combination differentiation therapy.
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影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
影响因子：
11.2
作者：
Bunaciu RP;Yen A
通讯作者：
Yen A
影响因子：
3.7
作者：
Bunaciu RP;Jensen HA;MacDonald RJ;LaTocha DH;Varner JD;Yen A
通讯作者：
Yen A
影响因子：
3.7
作者：
Barr MP;Gray SG;Hoffmann AC;Hilger RA;Thomale J;O'Flaherty JD;Fennell DA;Richard D;O'Leary JJ;O'Byrne KJ
通讯作者：
O'Byrne KJ
影响因子：
11.4
作者：
通讯作者：
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