Expression profiles of adult T-cell leukemia-lymphoma and associations with clinical responses to zidovudine and interferon alpha.
Expression profiles of adult T-cell leukemia-lymphoma and associations with clinical responses to zidovudine and interferon alpha.
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DOI：
10.3109/10428191003728628
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发表时间：
2010-07
影响因子：
2.6
通讯作者：
Lossos IS
中科院分区：
文献类型：
--
作者：
Alizadeh AA;Bohen SP;Lossos C;Martinez-Climent JA;Ramos JC;Cubedo-Gil E;Harrington WJ Jr;Lossos IS
成人T细胞白血病淋巴瘤（ATLL）是一种HTLV-1相关的淋巴增生性恶性肿瘤，通常是致命的。我们比较了9例ATLL患者在诊断时和齐多夫定（AZT）和干扰素α（IFNα）联合治疗后即刻的白血病标本的基因表达谱（GEP）。GEPs也与比较基因组杂交确定的遗传畸变有关。我们在mRNA水平上鉴定了ATLL白血病细胞中过度表达的几个基因，包括林恩、CSPG 2和LMO 2，并在蛋白水平上证实了ATLL细胞中LMO 2的表达。体内AZT-IFN α治疗引起干扰素诱导基因的显著诱导，伴随着细胞周期调控基因的抑制，包括编码核糖体蛋白的基因。值得注意的是，对AZT-IFNα无应答的患者与应答患者的最大差异在于这些相同的IFN应答基因的表达较低，以及抗原加工和呈递装置的组分。与AZT-IFNα治疗反应相关的特异性基因表达特征的证明可能为ATLL的作用机制提供新的见解。
Adult T-cell leukemia–lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from nine patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon α (IFNα). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2, and LMO2, and confirmed LMO2 expression in ATLL cells at the protein level. In vivo AZT–IFNα therapy evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycle regulated genes, including those encoding ribosomal proteins. Remarkably, patients not responding to AZT–IFNα differed most from responding patients in lower expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT–IFNα therapy may provide novel insights into the mechanisms of action in ATLL.
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DOI：
10.1073/pnas.88.10.4367
发表时间：
1991-05-01
影响因子：
11.1
作者：
BOEHM, T;FORONI, L;RABBITTS, TH
通讯作者：
RABBITTS, TH
影响因子：
11.4
作者：
INOUE, J;SEIKI, M;YOSHIDA, M
通讯作者：
YOSHIDA, M
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
20.3
作者：
Chung, EJ;Hwang, SG;Trepel, JB
通讯作者：
Trepel, JB
影响因子：
20.3
作者：
Martinez-Climent, JA;Alizadeh, AA;Lossos, IS
通讯作者：
Lossos, IS