Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML
Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML
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DOI：
10.1038/sj.leu.2402452
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发表时间：
2002-05-01
期刊：
影响因子：
11.4
通讯作者：
del Senno, L
中科院分区：
文献类型：
--
作者：
Gandini, D;De Angeli, C;del Senno, L
HTIF 1 α是一种转录辅激活因子，能够介导RAR α活性并与PML功能性相互作用，由染色体7 q32 -34上的基因编码，该基因是急性髓性白血病（AML）的关键区域。假设该基因可能与AML相关，我们研究了36例M1-M5 AML患者（28例“新发”和8例“继发于”骨髓增生异常综合征（MDS））白血病细胞中的HTIF 1 α DNA结构和RNA表达。未发现异常的HTIF 1 α DNA片段，而在染色体7 q32缺失和易位的患者中观察到HTIF 1 α DNA丢失，1例未检测到7号染色体异常。在急性髓细胞白血病原始细胞中发现了HTIF 1 α RNA，而在正常单核细胞中几乎检测不到。患者之间的表达各不相同; M1至M3亚型较高，M1中的值最高;在M4和M5 AML中持续观察到低水平。此外，HTIF 1 α在MDS相关AML（MDR-AML）中显著过表达，但在MDS中不表达。我们还发现HTIF 1 α在骨髓细胞系中表达较高。在髓母细胞HL 60和早幼粒细胞NB 4细胞中，TPA或维生素D3诱导分化为沿着单核-巨噬细胞途径，HTIF 1 α表达降低，而RA或DMSO诱导分化为粒细胞时，HTIF 1 α表达维持在高水平。在K562细胞中，高铁血红素诱导红系分化后，HTIF 1 α RNA水平没有变化。这些结果表明，HTIF 1 α可能在髓样分化中发挥作用，在造血谱系中受到明显调控。
HTIF1alpha, a transcription coactivator which is able to mediate RARalpha activity and functionally Interact with PML, is encoded by a gene on chromosome 7q32-34, which Is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1alpha DNA structure and RNA expression in leukemic cells from 36 M1-M5 AML patients (28 'de novo' and eight 'secondary' to myelodysplastic syndrome (MDS)). Abnormal HTIF1alpha DNA fragments were never found, whereas loss of HTIF1alpha DNA was observed in the patients with chromosome 7q32 deletion and translocation, and In one case without detectable chromosome 7 abnormality. HTIF1alpha RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients; higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1alpha was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1alpha expression was high In myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic-macrophage pathway by TPA or vitamin D3, HTIF1alpha expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1alpha RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1alpha could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages.