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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, pT , 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 pT transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half 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 double-positive (DP)
phenotype, in keeping with a population undergoing selection. Most
TCR T-ALLs were pT , terminal deoxynucleotidyl transferase (TdT), and RAG-1lo/neg,
double-negative/single-positive (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
proportion. As such they may correspond to TCR lineage precursors selected by TCR expression, to early  cells recently
derived from a pT + common  /
precursor, or to a lineage-deregulated  / intermediate. Approximately 30% of T-ALLs were sCD3/cTCR 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 , and RAG-1 low/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
that can aid in the understanding of healthy human T-cell development.

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