Abstract
ALL (Acute lymphoblastic leukemia) is the most common pediatric malignancy and T-ALL (T-cell acute lymphoblastic leukemia) comprises about 15% cases. Compared with B-ALL (B-cell acute lymphoblastic leukemia), the prognosis of T-ALL is poorer, the chemotherapy is easier to fail and the relapse rate is higher. Previous studies mainly focused in Notch1-related long non-coding RNAs (lncRNAs) in T-ALL. Here, we intend to investigate lncRNAs involved in T-ALL covering different subtypes. The lncRNA PPM1A-AS was screened out for its significant up-regulation in 10 T-ALL samples of different subtypes than healthy human thymus extracts. Besides, the PPM1A-AS expression levels in 3 T-ALL cell lines are markedly higher than that in CD45+ T cells of healthy human. We further demonstrate that PPM1A-AS can promote cell proliferation and inhibit cell apoptosis in vitro and can influence T-ALL growth in vivo. Finally, we verified that PPM1A-AS can regulate core proteins, Notch4, STAT3 and Akt, of 3 important signaling pathways related to T-ALL. These results confirm that lncRNA PPM1A-AS can act as an oncogene in T-ALL and maybe a potential clinical target of patients resistant to current chemotherapy or relapsed cases.
Highlights
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy induced by the transformation of T-cell progenitors [1]
To identify long non-coding RNAs (lncRNAs) differentially expressed in T-ALL, we collected and analyzed RNA sequencing (RNA-seq) data of 10 T-ALL patients and 2 human whole thymus extracts from public database (GSE110636 [13], GSE57982 [10], the sample numbers were listed in Supplementary Table 1)
Among these lncRNAs, we found that CTD-2184C24.2 (ENST00000553775) was obviously increased in T-ALL patients (Figure 1B)
Summary
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy induced by the transformation of T-cell progenitors [1]. LncRNA PPM1A-AS Regulate T-ALL Development acute lymphoblastic leukemia (cALL) causes the most frequent death from cancer in pediatrics [3]. Genetic alterations, including point mutations, chromosomal rearrangements and the loss or gain of chromosome, have been well studied due to the development of genome-wide sequencing. More than 10 mutated genes work together and lead to the transformation of T cells into aggressive leukemia cells with enhanced proliferation and survival characteristics, impaired differentiation, altered cell cycle and metabolism properties [5]. The screening out of novel molecules that participate in several regulating pathways may contribute to the clinical treatment of complex T-ALL cases which are resistant to given drugs or relapsed cases
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