Histone deacetylase inhibition improves differentiation of dendritic cells from leukemic blasts of patients with TEL/AML1-positive acute lymphoblastic leukemia
Histone deacetylase inhibition improves differentiation of dendritic cells from leukemic blasts of patients with TEL/AML1-positive acute lymphoblastic leukemia
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DOI：
10.1189/jlb.0808469
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发表时间：
2009-03-01
影响因子：
5.5
通讯作者：
Moldenhauer, Anja
中科院分区：
文献类型：
--
作者：
Schmidt, Kerstin;Seeger, Karl;Moldenhauer, Anja
组蛋白去乙酰化酶抑制剂（HdI）可能会促进白血病树突状细胞（DC）的分化。因此，在细胞因子TNF-α、GM-CSF、c-kit配体和胎肝酪氨酸激酶3配体中培养100例急性淋巴细胞白血病（ALL）儿童的骨髓样本，加或不加IL-3和IL-4，并在给予HdI丙戊酸（瓦尔）、辛二酰苯胺异羟肟酸（SAHA）、异丁酰胺或阿司他丁A后进行培养。在检测的样本中，25例为染色体易位t（12; 21）阳性，编码融合基因易位ETS样白血病/急性髓细胞白血病1（TEL/AML 1）。SAHA在无IL的条件下增加TEL/AML 1阳性原始细胞的CD 83表达，SAHA和瓦尔在IL存在的条件下增加CD 86（+）80（-）细胞的数量。瓦尔和异丁酰胺支持TEL/AML 1阳性的白血病DC的同种异体刺激能力;瓦尔和SAHA降低TEL/AML 1阴性DC的同种异体刺激能力。用白血病DC致敏的细胞毒性T细胞在呈递TEL/AML 1肽后产生更多的IFN-γ和TNF-α。它们还诱导未分化胚细胞的细胞毒性溶解，当加入瓦尔或SAHA后形成TEL/AML 1阳性DC时，这种溶解增强。因此，推荐使用HdI来区分白血病DC与TEL/AML 1阳性ALL患者。J.利瓦克85：563-573; 2009年。
Histone deacetylase inhibitors (HdI) could potentially improve the differentiation of leukemic dendritic cells (DC). Therefore, bone marrow samples from 100 children with acute lymphoblastic leukemia (ALL) were cultured in the cytokines TNF-alpha, GM-CSF, c-kit ligand, and fetal liver tyrosine kinase 3 ligand, with or without IL-3 and -4 and after administration of HdI valproic acid (VAL), suberoylanilide hydroxamic acid (SAHA), isobutyramid, or trichostatin A. Among the tested samples, 25 were positive for the chromosomal translocation t(12; 21), encoding the fusion gene translocation ETS-like leukemia/acute myeloid leukemia 1 (TEL/AML1). SAHA increased CD83 expression of TEL/AML1-positive blasts in conditions without ILs, and SAHA and VAL increased the number of CD86(+)80(-) cells in the presence of ILs. VAL and isobutyramid supported the allostimulatory capacities of TEL/AML1-positive, leukemic DC; VAL and SAHA reduced those of TEL/AML1-negative DC. Cytotoxic T cells sensitized with leukemic DC produced more IFN-gamma and TNF-alpha upon presentation of the TEL/AML1 peptide. They also induced the cytotoxic lysis of nondifferentiated blasts, which was enhanced when TEL/AML1-positive DC had developed after addition of VAL or SAHA. Therefore, the use of HdI in the differentiation of leukemic DC from patients with TEL/AML1-positive ALL is recommended. J. Leukoc. Biol. 85: 563-573; 2009.