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

被引:140
作者
Asnafi, V
Beldjord, K
Boulanger, E
Comba, B
Le Tutour, P
Estienne, MH
Davi, F
Landman-Parker, J
Quartier, P
Buzyn, A
Delabesse, E
Valensi, F
Macintyre, E
机构
[1] Hop Necker Enfants Malad, Hematol Lab, F-75743 Paris 15, France
[2] Hop La Pitie Salpetriere, Paris, France
[3] Hop Trousseau, F-75571 Paris, France
[4] Bretonneau Hosp, Tours, France
[5] CHU Necker Enfants Malad, AP HP, Dept Biol & Clin Hematol, Tours, France
关键词
D O I
10.1182/blood-2002-08-2438
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 TCRalphabeta 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 TCRgammadelta T-ALLs were pTalpha, terminal deoxynucleotidyl transferase (TdT), and RAG-1(lo/neg), double-negative/single-positive (DN/SP), and demonstrated only TCRbeta DJ rearrangement, whereas 40% were pTalpha, TdT, and RAG-1 positive, DIP, and demonstrated TCRbeta V(D)J rearrangement, with cTCRbeta expression in proportion. As such they may correspond to TCRalphabeta lineage precursors selected by TCRgammadelta expression, to early gammadelta cells recently derived from a pTalpha(+) common alphabeta/gammadelta precursor, or to a lineage-deregulated alphabeta/gammadelta 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.
引用
收藏
页码:2693 / 2703
页数:11
相关论文
共 66 条
  • [1] Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells
    Allman, D
    Karnell, FG
    Punt, JA
    Bakkour, S
    Xu, LW
    Myung, P
    Koretzky, GA
    Pui, JC
    Aster, JC
    Pear, WS
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (01) : 99 - 106
  • [2] Dendritic cells and the control of immunity
    Banchereau, J
    Steinman, RM
    [J]. NATURE, 1998, 392 (6673) : 245 - 252
  • [3] Barber DF, 1998, J IMMUNOL, V161, P11
  • [4] Combined expression of pTα and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis
    Bellavia, D
    Campese, AF
    Checquolo, S
    Balestri, A
    Biondi, A
    Cazzaniga, G
    Lendahl, U
    Fehling, HJ
    Hayday, AC
    Frati, L
    von Boehmer, H
    Gulino, A
    Screpanti, I
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) : 3788 - 3793
  • [5] The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias
    Bene, MC
    Bernier, M
    Casasnovas, RO
    Castoldi, G
    Knapp, W
    Lanza, F
    Ludwig, WD
    Matutes, E
    Orfao, A
    Sperling, C
    van't Veer, MB
    [J]. BLOOD, 1998, 92 (02) : 596 - 599
  • [6] BENE MC, 1995, LEUKEMIA, V9, P1783
  • [7] T cell precursors in man and mice
    Blom, B
    Res, PCM
    Spits, H
    [J]. CRITICAL REVIEWS IN IMMUNOLOGY, 1998, 18 (04) : 371 - 388
  • [8] Blom B, 1999, BLOOD, V93, P3033
  • [9] Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia
    Boeckx, N
    Willemse, MJ
    Szczepanski, T
    van der Velden, VHJ
    Langerak, AW
    Vandekerckhove, P
    van Dongen, JJM
    [J]. LEUKEMIA, 2002, 16 (03) : 368 - 375
  • [10] BMA031, A MONOCLONAL-ANTIBODY SUITED TO IDENTIFY THE T-CELL RECEPTOR ALPHA-BETA/CD3 COMPLEX ON VIABLE HUMAN LYMPHOCYTES-T IN NORMAL AND DISEASE STATES
    BORST, J
    VANDONGEN, JJM
    DEVRIES, E
    COMANSBITTER, WM
    VANTOL, MJD
    VOSSEN, JM
    KURRLE, R
    [J]. HUMAN IMMUNOLOGY, 1990, 29 (03) : 175 - 188