Identification of a leukemic counterpart of the plasmacytoid dendritic cells.
This work aims to demonstrate that CD4(+)CD56(+) malignancies arise from transformed cells of the lymphoid-related plasmacytoid dendritic cell (pDC) subset. The analysis of malignant cells from 7 patients shows that in all cases, like pDCs, leukemic cells are negative for lineage markers CD3, CD19, CD13, CD33, and CD11c but express high levels of interleukin-3 receptor alpha chain (IL-3Ralpha), HLA-DR, and CD45RA. Tumor cells produce interferon-alpha in response to influenza virus, while upon maturation with IL-3 they become a powerful inducer of naive CD4(+) T-cell proliferation and promote their T-helper 2 polarization. As pDCs, leukemic cells also express pre-Talpha and lambda-like 14.1 transcripts, arguing in favor of a lymphoid origin. In addition, malignant cells express significant levels of CD56 and granzyme B. Overall, those observations suggest that CD4(+)CD56(+) leukemic cells could represent the malignant counterpart of pDCs, both of which are closely related to B, T, and NK cells.
Chaperot
L
L
Department of Research and Development, Research Group on Lymphoma, EFS Rhône-Alpes Grenoble, La Tronche, France. laurence.chaperot@efs.sante.fr
Bendriss
N
N
Manches
O
O
Gressin
R
R
Maynadie
M
M
Trimoreau
F
F
Orfeuvre
H
H
Corront
B
B
Feuillard
J
J
Sotto
J J
JJ
Bensa
J C
JC
Brière
F
F
Plumas
J
J
Jacob
M C
MC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000032:analysis; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D019002:CD56 Antigen / Q000032:analysis; D002454:Cell Differentiation; D002648:Child; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D053804:Granzymes; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016185:Receptors, Interleukin-3 / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D019013:CD40 Antigens; D019002:CD56 Antigen; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases