Oksa Laura, Mäkinen Artturi, Nikkilä Atte, Hyvärinen Noora, Laukkanen Saara, Rokka Anne, Haapaniemi Pekka, Seki Masafumi, Takita Junko, Kauko Otto, Heinäniemi Merja, Lohi Olli
Tampere Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, FI-33520 Tampere, Finland.
Fimlab Laboratories, Department of Pathology, Tampere University Hospital, FI-33520 Tampere, Finland.
Cancers (Basel). 2022 Apr 26;14(9):2169. doi: 10.3390/cancers14092169.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.
T细胞急性淋巴细胞白血病(T-ALL)是一种侵袭性血液恶性肿瘤,目前尚无成熟的预后生物标志物。我们检测了血液恶性肿瘤中蛋白质精氨酸甲基转移酶的表达,发现T-ALL中该酶的mRNA水平很高,尤其是在T-ALL的成熟亚型中。通过CRISPR-Cas9对其进行基因敲除可减少T-ALL细胞的集落形成,并改变与RNA和DNA加工以及T-ALL发病机制相关的蛋白质复合物中的精氨酸单甲基化模式。其中包括RUNX1,其靶基因表达因此失调。这些结果表明PRMT7在T-ALL的发病机制中起积极作用。