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

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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2693-2703

IMMUNOBIOLOGY

Analysis of TCR, pTalpha , and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment

Vahid Asnafi, Kheira Beldjord, Emmanuelle Boulanger, Béatrice Comba, Patricia Le Tutour, Marie-Hélène Estienne, Frédéric Davi, Judith Landman-Parker, Pierre Quartier, Agnès Buzyn, Eric Delabesse, Françoise Valensi, and Elizabeth Macintyre

From the Department of Biological and Clinical Hematology, Centre Hospitalier-Universitaire/Assistance Publique-Hopitaux de Paris (CHU/AP-HP) Necker-Enfants Malades and Université Paris V; Hôpital Bretonneau, Tours; Hôpital La Pitié-Salpêtrière and Hôpital Trousseau, Paris, France.

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 pTalpha transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half the TCRalpha beta lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pTalpha , and cTCRbeta expression, absence of TCRdelta deletion, and a sCD3-, CD1a+, CD4/8 double-positive (DP) phenotype, in keeping with a population undergoing beta  selection. Most TCRgamma delta T-ALLs were pTalpha , terminal deoxynucleotidyl transferase (TdT), and RAG-1lo/neg, double-negative/single-positive (DN/SP), and demonstrated only TCRbeta DJ rearrangement, whereas 40% were pTalpha , TdT, and RAG-1 positive, DP, and demonstrated TCRbeta V(D)J rearrangement, with cTCRbeta expression in proportion. As such they may correspond to TCRalpha beta lineage precursors selected by TCRgamma delta expression, to early gamma delta cells recently derived from a pTalpha + common alpha beta /gamma delta precursor, or to a lineage-deregulated alpha beta /gamma delta intermediate. Approximately 30% of T-ALLs were sCD3/cTCRbeta - 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, pTalpha , and RAG-1 low/negative, despite immature TCRdelta and TCRgamma 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.

© 2003 by The American Society of Hematology.
 

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