The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells.
The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells.
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FAMLF 选择性剪接变体的共有序列在未分化造血细胞中过度表达
DOI：
10.1590/1414-431x20154430
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Wang SY
中科院分区：
文献类型：
--
作者：
Chen WL;Luo DF;Gao C;Ding Y;Wang SY
家族性急性髓性白血病相关因子基因（FAMLF）先前从家族性AML消减cDNA文库中鉴定，并显示经历选择性剪接。本研究采用实时荧光定量PCR方法检测了119例初发急性白血病（AL）患者和104例健康对照者外周血单个核细胞（PBMC）以及12例AL患者和10例健康供者的CD 34+细胞中FAMLF选择性剪接转录共有序列（FAMLF-CS）的表达。从一个新的剪接变异体的FAMLF的429 bp的片段，并有针对性的363 bp的共识序列，以量化总FAMLF表达。采用Kruskal-Wallis、Nemenyi、斯皮尔曼相关性和Mann-Whitney U检验分析数据。FAMLF-CS在AL患者PBMCs、CD 34+细胞和对照组中的表达均显著高于对照组（P<0.0001）。AML组PBMC中FAMLF-CS表达与红细胞计数呈正相关（rs =0.317，P=0.006），血红蛋白水平（rs =0.210，P=0.049），外周血原始细胞百分比（rs =0.256，P=0.027），但与对照组血红蛋白水平呈负相关（rs =-0.391，P<0.0001）。CD 34+高表达的AML患者FAMLF-CS表达明显高于CD 34+低表达的AML患者（P=0.041）。我们的研究结果表明，FAMLF在正常和恶性的未成熟造血细胞中高表达，但在正常成熟的PBMC中表达较低。
The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover,FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs =0.210, P=0.049), and percentage of peripheral blood blasts (rs =0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs =–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higherFAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed thatFAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.