title: CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features.
abstract: Most lymphoblastic lymphomas (LBLs) are regarded as neoplasms of immature T cells because they express cytoplasmic CD3 and frequently carry T-cell receptor (TCR) gene rearrangements. Immature natural killer (NK) and T cells, however, have a common bipotent T/NK-cell precursor in the thymus, and NK cells also express cytoplasmic CD3. Thus, some LBLs could arise from immature NK cells. Mature NK cells express 2 CD94 transcripts: 1A, induced by interleukin 15 (IL-15), and 1B constitutively. Because immature NK cells require IL-15 for development, CD94 1A transcripts could be a marker of NK-LBL. To test this hypothesis, we used laser capture microdissection to isolate IL-15 receptor alpha(+) lymphoid cells from the thymus and showed that these cells contained CD94 1A transcripts. We then assessed for CD94 transcripts in 21 cases of LBL that were cytoplasmic CD3(+), nuclear terminal deoxynucleotidyl transferase positive (TdT(+)), and CD56(-), consistent with either the T-cell or NK-cell lineage. We found that 7 LBLs expressed CD94 1A transcripts without TCR gene rearrangements, suggesting NK-cell lineage. Patients with NK-LBL were younger than patients with T-LBL (15 years versus 33 years; P = .11) and had a better 2-year survival (100% versus 27%; P < .01). These results improve the current classification of LBL and contribute to our understanding of NK-cell differentiation.
authors.affiliation: Department of Pathology, National Taiwan University College of Medicine, Taipei.
authors.forename: Chung-Wu
authors.initials: CW
authors.lastname: Lin
authors.forename: Ting-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Shee-Uan
authors.initials: SU
authors.lastname: Chen
authors.forename: Kun-Teng
authors.initials: KT
authors.lastname: Wang
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D007938:Leukemia / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology
chemical_list: D017252:CD3 Complex; C508024:IL15RA protein, human; D019409:Interleukin-15; C497869:KLRD1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011948:Receptors, Antigen, T-Cell; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2