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

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 pTα transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid dev...

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Bibliographic Details
Published in:Blood 2003-04, Vol.101 (7), p.2693-2703
Main Authors: 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
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antigens, CD - analysis
Biological and medical sciences
Cell Lineage
Child
Genotype
Hematologic and hematopoietic diseases
Homeodomain Proteins - genetics
Humans
Immunophenotyping
Leukemia-Lymphoma, Adult T-Cell - classification
Leukemia-Lymphoma, Adult T-Cell - immunology
Leukemia-Lymphoma, Adult T-Cell - pathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Membrane Glycoproteins - genetics
Middle Aged
Receptors, Antigen, T-Cell - classification
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
RNA, Messenger - analysis
T-Lymphocytes - cytology
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Summary: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 pTα transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half the TCRαβ lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pTα, and cTCRβ expression, absence of TCRδ deletion, and a sCD3−, CD1a+, CD4/8 double-positive (DP) phenotype, in keeping with a population undergoing β selection. Most TCRγδ T-ALLs were pTα, terminal deoxynucleotidyl transferase (TdT), and RAG-1lo/neg, double-negative/single-positive (DN/SP), and demonstrated only TCRβ DJ rearrangement, whereas 40% were pTα, TdT, and RAG-1 positive, DP, and demonstrated TCRβ V(D)J rearrangement, with cTCRβ expression in proportion. As such they may correspond to TCRαβ lineage precursors selected by TCRγδ expression, to early γδ cells recently derived from a pTα+common αβ/γδ precursor, or to a lineage-deregulated αβ/γδ intermediate. Approximately 30% of T-ALLs were sCD3/cTCRβ−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, pTα, and RAG-1 low/negative, despite immature TCRδ and TCRγ 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2002-08-2438