Journal
FRONTIERS IN ONCOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2019.01058
Keywords
miR-340; acute myeloid leukemia; clinical outcome; chemotherapy; allo-HCST
Categories
Funding
- National Natural Science Foundation of China [81670142, 81772658, 81870163, 81700179, 81700199]
- Jiangsu Provincial Key Research and Development Program [BE2017638, BE2017636]
- Natural Science Foundation of Jiangsu Province [BK20180104, BK20151153, BK20160226]
- Foundation of Jiangsu Province Six Talents Peak [2017-WSN-120]
- Xuzhou Key Research and Application of Basic Research Projects [KC17158]
- Postgraduate Research and Practice Innovation Program of Jiangsu Province [SJCX18_0704, SJKY19_2110]
- Natural Science Foundation of Jiangsu higher education institutions [16KJA320003]
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Acute myeloid leukemia (AML) requires refined risk stratification tools to drive decisions concerning effective therapeutic strategies. Here, genome-wide screening was carried out for identifying miRNA molecules capable of predicting treatment outcome in AML patients based on the TCGA dataset. We identified miR-340 as a prognostic factor for selecting treatment between chemotherapy and allogeneic transplantation (allo-HSCT). In multivariable analyses, low miR-340 expression independently predicted reduced OS (HR = 2.07, P = 0.004) and EFS (HR = 1.909, P = 0.01) independent of other well-known prognostic factors. Meanwhile, allo-HSCT overcome deleterious outcomes related to low miR-340. Cases administered allo-HSCT showed markedly improved OS (HR = 0.316, P < 0.0001) and EFS (HR = 0.391, P = 0.002) in comparison with those receiving chemotherapy in the low miR-340 group. Gene expression assessment revealed that elevated miR-340 amounts were negatively correlated with HOXA/HOXB cluster levels, as well as the amounts of the HOX cofactor MEIS1. Strikingly, in silico analysis pointing to HOXA10, HOXB2, and MEIS1 as miR-340 targets. The miR-340 expression may help identify cases requiring strategies for selecting the optimal therapeutic option between chemotherapy and allo-HCST. AML cases showing low miR-340 levels should be strongly considered for early allo-HSCT treatment.
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