Haouas Houda, Haouas Samira, Uzan Georges, Hafsia Aïcha
Department of Biological and Chemical Engineering, National Institute of Applied Sciences and Technology, Tunis, Tunisia.
Hematology. 2010 Aug;15(4):193-203. doi: 10.1179/102453310X12647083620769.
The heterogeneity of acute myeloid leukemia (AML) with respect to biology and clinical course resides in the fact that patients belonging to the same group show marked differences in their response to chemotherapy, necessitating a refinement of AML classification.
In order to define molecular markers for AML, we performed microarray analysis on peripheral blood cells from two M5 AML patients, and selected four differentially expressed genes to validate their expression by real-time quantitative PCR (RT-PCR).
We have shown that two downregulated genes in AML, those encoding guanine nucleotide-binding protein gamma11 (GNG11) and amphiregulin (AREG), are also downregulated in B-lineage acute lymphoblastic leukemia (B-ALL) and T-lineage acute lymphoblastic leukemia (T-ALL) patients. A second gene, that encoding ceruloplasmin (CP), is upregulated in AML but not in B-ALL and T-ALL. The level of expression of these genes varies from one patient to another.
Since the number of patients studied is limited, further studies are needed with a larger series of patients to evaluate the potential utility of GNG11, AREG and CP as molecular markers for AML subtype classification. Our study is the first to analyze these genes in AML, B-ALL, T-ALL and chronic leukemia (myeloid and lymphoid) patients by RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukemia.
急性髓系白血病(AML)在生物学和临床病程方面存在异质性,这表现为属于同一组的患者对化疗的反应存在显著差异,因此需要对AML分类进行细化。
为了确定AML的分子标志物,我们对两名M5型AML患者的外周血细胞进行了微阵列分析,并选择了四个差异表达基因,通过实时定量PCR(RT-PCR)验证其表达情况。
我们发现AML中两个下调的基因,即编码鸟嘌呤核苷酸结合蛋白γ11(GNG11)和双调蛋白(AREG)的基因,在B系急性淋巴细胞白血病(B-ALL)和T系急性淋巴细胞白血病(T-ALL)患者中也下调。另一个基因,即编码铜蓝蛋白(CP)的基因,在AML中上调,但在B-ALL和T-ALL中未上调。这些基因的表达水平在不同患者之间有所不同。
由于所研究的患者数量有限,需要对更多患者进行进一步研究,以评估GNG11、AREG和CP作为AML亚型分类分子标志物的潜在效用。我们的研究首次通过RT-PCR分析了AML、B-ALL、T-ALL和慢性白血病(髓系和淋巴系)患者中的这些基因。这种快速且灵敏的方法可用于在不同类型白血病中筛选这些基因。