Expression of autophagy genes in acute myeloid leukemia: associations with clinical characteristics and prognosis

Abstract

The relationships between autophagy-associated gene expression and clinical characteristics and prognosis in acute myeloid leukemia (AML) have not been well revealed. We examined mRNA expression of Bcl-2, p62, Beclin 1, VPS34, Rubicon, ALFY, UVRAG, ULK1, LC3 and NBR1 in 20 AML cases and 10 benign hematological cases by real-time PCR. Clinical information, treatment responses and outcomes of the AML patients were collected. Beclin 1, LC3, UVRAG, Rubicon and NBR1 were downregulated in AML patients compared with control group (P<0.05). Low ULK1 expression was associated with high white blood cell counts (P<0.05). Autophagy-associated gene expression was not correlated with chemotherapy response. Finally, we analyzed overall survival and found no obvious association with gene expression. However, in unfavorable outcome patients, low Beclin 1 and p62 expression showed worse overall survival than high-expression. Autophagy genes are associated with outcome in AML patients and may be biomarkers or targets in the future.

The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy

“…RUBICON expression is significantly decreased in AML cases compared with control group 33 . Accordingly, an involvement of autophagy pathway in the outcome of AML leukemia has been suggested.…”

Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia

“…In neoplastic cells however, autophagy sustains survival and proliferation upon exposure to intracellular and environmental stress, hence supporting tumor growth, invasion, and metastatic dissemination 6 . The deregulation of autophagy has been reported in AML [7][8][9][10] . Historical and new treatments have been shown to induce autophagy, which may be protective or participate in cell death depending on the compound [11][12][13][14] .…”

NPM1 mutant maintains ULK1 protein stability via TRAF6‐dependent ubiquitination to promote autophagic cell survival in leukemia

“…Unfortunately, this would result in only a few patients being enrolled in our study, and the statistical power could, therefore, be significantly reduced. Of note, Liang et al 43 also observed a trend toward higher ULK1 mRNA levels in the AML patients compared with the patients with benign hematological diseases. Subsequently, we centered on the molecular mechanism underlying ULK1 high expression in NPM1-mutated AML.…”