Leukemia-propagating cells demonstrate distinctive gene expression profiles compared with other cell fractions from patients with de novo Philadelphia chromosome-positive ALL
Leukemia-propagating cells demonstrate distinctive gene expression profiles compared with other cell fractions from patients with de novo Philadelphia chromosome-positive ALL
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与新发费城染色体阳性 ALL 患者的其他细胞组分相比，白血病增殖细胞表现出独特的基因表达谱
DOI：
10.1007/s00277-018-3253-5
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发表时间：
2018-02
影响因子：
3.5
通讯作者：
Yuan Kong
中科院分区：
文献类型：
--
作者：
Hong-Yan Zhao;Yang Song;Xie-Na Cao;Ya-Zhen Qin;Yue-Yun Lai;Hao Jiang;Qian Jiang;Xiao-Jun Huang;Yuan Kong
费城染色体阳性急性淋巴细胞白血病（Ph+ALL）患者异基因造血干细胞移植后复发仍是主要障碍之一。白血病增殖细胞（LPC）的持续存在可能导致Ph+ALL的复发。使用异种移植物试验，最近发现Ph+ALL中的CD 34 + CD 38 − CD 58 −组分中的LPC富集。进一步的队列研究表明，诊断时的LPC表型是Ph+ALL复发的独立风险因素。然而，对LPC介导复发的潜在分子机制知之甚少。因此，使用RNA测序（RNA-Seq）研究了来自新发Ph+ALL患者的分选LPC和其他细胞组分的基因表达谱。通过基因本体（GO）富集和京都基因与基因组百科全书（KEGG）分析，发现LPC与其他细胞组分之间的差异表达基因大多与细胞周期和代谢的调控有关。与RNA-Seq结果一致，细胞周期相关基因（如细胞周期蛋白依赖性激酶4）的mRNA水平在LPC组分中显著低于其他细胞组分。此外，静止细胞在LPC中的比例显着高于其他细胞组分。总之，在原发性Ph+ALL患者的LPC和其他细胞组分之间，证明了主要与细胞周期和代谢调控相关的独特基因表达谱和基因簇。因此，为Ph+ALL患者开发新的基于LPC的治疗策略将是有益的。
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph+ALL. Using a xenograft assay, LPCs enrichment in the CD34+CD38−CD58−fraction in Ph+ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph+ALL. However, little is known about the potential molecular mechanism of LPCs-mediated relapse. Therefore, the gene expression profiles of the sorted LPCs and other cell fractions from patients with de novo Ph+ALL were investigated using RNA sequencing (RNA-Seq). Most of the differentially expressed genes between the LPCs and other cell fractions were related to the regulation of the cell cycle and metabolism, as identified by the gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Consistent with the RNA-Seq results, the mRNA levels of cell cycle-related genes, such as cyclin-dependent kinase 4, were significantly lower in the LPCs fraction than in other cell fractions. Moreover, the proportion of quiescent cells in LPCs was significantly higher than in other cell fractions. In summary, distinctive gene expression profiles and clusters, which were mostly related to the regulation of the cell cycle and metabolism, were demonstrated between LPCs and other cell fractions from patients with de novo Ph+ALL. Therefore, it would be beneficial to develop novel LPCs-based therapeutic strategies for Ph+ALL patients.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
23.9
作者：
Lagadinou, Eleni D.;Sach, Alexander;Callahan, Kevin;Rossi, Randall M.;Neering, Sarah J.;Minhajuddin, Mohammad;Ashton, John M.;Pei, Shanshan;Grose, Valerie;O'Dwyer, Kristen M.;Liesveld, Jane L.;Brookes, Paul S.;Becker, Michael W.;Jordan, Craig T.
通讯作者：
Jordan, Craig T.
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
DOI：
10.1038/leusup.2012.7
发表时间：
2012-08
期刊：
Leukemia supplements
影响因子：
--
作者：
OG Ottmann
通讯作者：
OG Ottmann
影响因子：
82.9
作者：
Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
通讯作者：
Dick, John E.