In:
Blood, American Society of Hematology, Vol. 101, No. 7 ( 2003-04-01), p. 2693-2703
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood-2002-08-2438
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2003
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
