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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-08-2438.

Submitted August 9, 2002
Accepted November 3, 2002
Analysis of TCR, pT and RAG-1 in T acute lymphoblastic leukemias improves understanding of early human T lymphoid lineage commitment
Vahid Asnafi, Kheira Beldjord, Emmanuelle Boulanger, Beatrice Comba, Patricia Le Tutour, Marie-Helene Estienne, Frederic Davi, Judith Landman-Parker, Pierre Quartier, Agnes Buzyn, Eric Delabesse, Francoise Valensi, and Elizabeth Macintyre*
Department of Clinical and Biological Hematology, CHU / AP-HP Necker-Enfants Malades and Paris V University, Paris, France
Department of Hematology, Hospital Bretonneau, Tours, France
Department of Hematology, Hospital La Pitie-Salpetriere, Paris, France
Department of Hematology, Hospital Trousseau, Paris, France
* Corresponding author; email: elizabeth.macintyre{at}nck.ap-hop-paris.fr.
T Acute Lymphoblastic Leukemias derive from human T lymphoid precursors arrested at various early stages of development. Correlation of phenotype and TCR status with RAG-1 and pT transcription in 114 T-ALLs demonstrated that they largely reflect physiological T lymphoid development. Half of the TCR lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pT and cTCR expression, absence of TCR deletion, and a sCD3-, CD1a+, CD4/8 DP phenotype, in keeping with a population undergoing selection. The majority of TCR T-ALLs were pT , TdT and RAG-1lo/neg, DN/SP and demonstrated only TCR DJ rearrangement, whereas 40% were pT , TdT and RAG-1 positive, DP and demonstrated TCR V(D)J rearrangement, with cTCR expression in a proportion. As such they are likely to correspond either to TCR lineage precursors selected by TCR expression or to early  cells, recently derived from a pT + common  / precursor,or to a lineage deregulated  / intermediate population. Approximately 30% of T-ALLs were sCD3/cTCR negative and corresponded to non-restricted thymic precursors since they expressed non T restricted markers such as CD34, CD13, CD33 and/or CD56 and were predominantly DN, CD1a, pT and RAG-1 negative, despite immature TCR and TCR rearrangements. TCR gene configuration identified progressive T lymphoid restriction. T-ALLs therefore provide homogeneous expansions of minor human lymphoid precursor populations which can clarify comprehension of normal human T cell development.

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