Badie Christophe, Blachowicz Agnieszka, Barjaktarovic Zarko, Finnon Rosemary, Michaux Arlette, Sarioglu Hakan, Brown Natalie, Manning Grainne, Benotmane M Abderrafi, Tapio Soile, Polanska Joanna, Bouffler Simon D
Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, UK.
Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Techology, Gliwice, Poland.
Oncotarget. 2016 Jun 28;7(26):40461-40480. doi: 10.18632/oncotarget.9626.
A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/in vivo passage material respectively, with one common to all materials. In cell lines, approximately 50% of the transcriptome changes are related to adaptation to cell culture, and in the proteome this proportion was higher. An AML 'signature' of 17 genes/proteins commonly deregulated in primary AMLs and cell lines compared to HPSCs was identified and validated using human AML transcriptome data. This also distinguishes primary AMLs from cell lines and includes proteins such as Coronin 1, pontin/RUVBL1 and Myeloperoxidase commonly implicated in human AML. C-Myc was identified as having a key role in radiation leukaemogenesis. These data identify novel candidates relevant to mouse radiation AML pathogenesis, and confirm that pathways of leukaemogenesis in the mouse and human share substantial commonality.
本文报道了对小鼠辐射诱导的急性髓系白血病（AML）进行的转录组和蛋白质组联合分析，研究使用了两种原发性AML、源自这些原发性AML的细胞系、另一种细胞系及其体内传代细胞。与造血祖细胞和干细胞（HPSC）相比，共鉴定出5000多个转录组改变，其中2600个在所有材料中均存在。在细胞系的蛋白质组中分别检测到55个改变，在原发性/体内传代材料的蛋白质组中检测到3个改变，所有材料中有一个共同改变。在细胞系中，约50%的转录组变化与细胞培养适应性有关，在蛋白质组中这一比例更高。通过与HPSC比较，在原发性AML和细胞系中共同失调的17个基因/蛋白质的AML“特征”被鉴定出来，并使用人类AML转录组数据进行了验证。这也将原发性AML与细胞系区分开来，包括通常与人类AML相关的蛋白质，如冠蛋白1、桥粒蛋白/RUVBL1和髓过氧化物酶。C-Myc被确定在辐射白血病发生中起关键作用。这些数据确定了与小鼠辐射AML发病机制相关的新候选物，并证实小鼠和人类白血病发生途径有很大的共性。
