Asnafi Vahid, Beldjord Kheira, Boulanger Emmanuelle, Comba Béatrice, Le Tutour Patricia, Estienne Marie-Hélène, Davi Frédéric, Landman-Parker Judith, Quartier Pierre, Buzyn Agnès, Delabesse Eric, Valensi Françoise, Macintyre Elizabeth
Department of Biological and Clinical Hematology, Centre Hospitalier-Universitaire/Assistance Publique-Hopitaux de Paris (CHU/AP-HP) Necker-Enfants Malades and Université Paris V, France.
Blood. 2003 Apr 1;101(7):2693-703. doi: 10.1182/blood-2002-08-2438. Epub 2002 Nov 21.
T-acute lymphoblastic leukemias (T-ALLs) derive from human T-lymphoid precursors arrested at various early stages of development. Correlation of phenotype and T-cell receptor (TCR) status with RAG-1 and pT alpha transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half the TCR alpha beta lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pT alpha, and cTCR beta expression, absence of TCR delta deletion, and a sCD3(-), CD1a(+), CD4/8 double-positive (DP) phenotype, in keeping with a population undergoing beta selection. Most TCR gamma delta T-ALLs were pT alpha, terminal deoxynucleotidyl transferase (TdT), and RAG-1(lo/neg), double-negative/single-positive (DN/SP), and demonstrated only TCR beta DJ rearrangement, whereas 40% were pT alpha, TdT, and RAG-1 positive, DP, and demonstrated TCR beta V(D)J rearrangement, with cTCR beta expression in proportion. As such they may correspond to TCR alpha beta lineage precursors selected by TCR gamma delta expression, to early gamma delta cells recently derived from a pT alpha(+) common alpha beta/gamma delta precursor, or to a lineage-deregulated alpha beta/gamma delta intermediate. Approximately 30% of T-ALLs were sCD3/cTCR beta(-) and corresponded to nonrestricted thymic precursors because they expressed non-T-restricted markers such as CD34, CD13, CD33, and CD56 and were predominantly DN, CD1a, pT alpha, and RAG-1 low/negative, despite immature TCR delta and TCR gamma rearrangements. TCR gene configuration identified progressive T-lymphoid restriction. T-ALLs, therefore, provide homogeneous expansions of minor human lymphoid precursor populations that can aid in the understanding of healthy human T-cell development.
T 细胞急性淋巴细胞白血病（T-ALL）起源于发育早期不同阶段停滞的人类 T 淋巴细胞前体。对 114 例 T-ALL 中表型、T 细胞受体（TCR）状态与重组激活基因 1（RAG-1）和前 T 细胞α链（pTα）转录的相关性研究表明，它们在很大程度上反映了生理性 T 淋巴细胞发育。一半的 TCRαβ谱系 T-ALL 表达前 TCR，RAG-1、pTα和 cTCRβ表达、TCRδ缺失的缺乏以及 sCD3(-)、CD1a(+)、CD4/8 双阳性（DP）表型证明了这一点，这与正在经历β选择的群体一致。大多数 TCRγδ T-ALL 是 pTα、末端脱氧核苷酸转移酶（TdT）和 RAG-1(低/阴性)、双阴性/单阳性（DN/SP），并且仅表现出 TCRβ DJ 重排；而 40%是 pTα、TdT 和 RAG-1 阳性、DP，并表现出 TCRβ V(D)J 重排，cTCRβ表达成比例。因此，它们可能对应于由 TCRγδ表达选择的 TCRαβ谱系前体、最近源自 pTα(+)共同αβ/γδ前体 的早期γδ细胞，或对应于谱系失调的αβ/γδ中间体。大约 30%的 T-ALL 是 sCD3/cTCRβ(-)，对应于非限制性胸腺前体，因为它们表达非 T 限制性标志物，如 CD34、CD13、CD33 和 CD56，并且尽管 TCRδ和 TCRγ重排不成熟，但主要是 DN、CD1a、pTα和 RAG-1 低/阴性。TCR 基因构型确定了渐进性 T 淋巴细胞限制。因此，T-ALL 提供了少量人类淋巴细胞前体群体的同质扩增，有助于理解健康人类 T 细胞的发育。
