Identification of genes potentially involved in disease transformation of CML

Identification of genes potentially involved in disease transformation of CML
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DOI:
10.1038/sj.leu.2403735
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发表时间:
2005-06-01
期刊:
影响因子:
11.4
通讯作者:
Ossenkoppele, GJ
Ossenkoppele, GJ
中科院分区:
医学1区
文献类型:
--
作者:
Janssen, JJWM;Klaver, SM;Ossenkoppele, GJ

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对于未达到(接近)完全细胞遗传学反应的慢性粒细胞白血病 (CML) 患者,该疾病会在几年内从惰性慢性阶段进展为快速致命的急变期。导致这一转变过程的事件在很大程度上是未知的。为了确定疾病过程中发生的基因表达变化,我们对连续储存的外周血单核细胞沉淀物进行了 cDNA 消减,这些沉淀物是在单个 CML 患者的整个疾病过程中收集的。总共鉴定出 32 个差异表达序列,其中 27 个对应于已知基因。在定量 PCR 中,其中 8 个基因(YWHAZ、GAS2、IL8、IL6、PBEF1、CCL4、SAT 和 MMRN)在其他 CML 患者样本中显示出相当的差异表达。这组基因可以被视为进一步研究 CML 疾病转化原因的起点,并可能导致治疗耐药 CML 的新靶点。
In patients with chronic myeloid leukemia (CML) who do not reach a ( near) complete cytogenetic response, the disease progresses over several years from an indolent, chronic phase into a rapidly fatal blast crisis. Events that are responsible for this transformation process are largely unknown. To identify changes in gene expression that occurred during the course of the disease, we performed cDNA subtraction on sequentially stored peripheral blood mononuclear cell pellets, collected throughout the course of disease of a single CML patient. In total, 32 differentially expressed sequences were identified, of which 27 corresponded to known genes. On quantitative PCR, eight of these genes, YWHAZ, GAS2, IL8, IL6, PBEF1, CCL4, SAT and MMRN, showed comparable differential expression in additional CML patient samples. This set of genes can be considered as a starting point for further research on causes of disease transformation in CML and may lead to new targets in the treatment of resistant CML.