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Blood, 1 February 2002, Vol. 99, No. 3, pp. 1030-1037
NEOPLASIA
Distinctive features of "nurselike" cells that differentiate
in the context of chronic lymphocytic leukemia
Nobuhiro Tsukada,
Jan A. Burger,
Nathan J. Zvaifler, and
Thomas J. Kipps
From the Department of Medicine, Division of
Hematology/Oncology, and Division of Rheumatology, Allergy, and
Immunology, University of California, San Diego, La Jolla, and
Department of Medicine, Freiburg University, Germany.
A subset of blood mononuclear cells from patients with chronic
lymphocytic leukemia (CLL) can differentiate in vitro into "nurselike" cells (NLCs) that can protect CLL cells from apoptosis. NLCs express cytoplasmic vimentin and stromal-derived factor 1 (SDF-1). NLCs also express CD14, as well as CD11b, CD33, CD40, CD45RO,
CD68, CD80, CD86, HLA-DQ, and HLA-DR, but not CD1a, CD2, CD3, CD11c,
CD19, CD45RA, CD83, CD106, or CD154. Consistent with this phenotype,
NLCs failed to differentiate from blood mononuclear cells that were
depleted of CD14+ cells or from isolated CD19+
cells. CD14+ blood cells of healthy donors could
differentiate into cells with the morphology and phenotype of NLCs when
cultured in direct contact with CLL B cells, but not with normal B
cells. Despite expressing antigens in common with blood monocytes,
monocyte-derived dendritic cells, and macrophages, NLCs expressed
significantly higher levels of CD68 than these other cell types.
Consistent with the notion that NLCs are present in vivo,
CD14+ splenocytes from CLL patients have NLC morphology and
express significantly higher levels of CD68 than CD14+
splenocytes from persons without known B-cell malignancy. These findings indicate that although NLCs may differentiate from blood monocytes, they probably represent a distinctive hematopoietic cell
type that exists in vivo, differentiates from hematopoietic CD14+ cells in the context of CLL, and in turn protect CLL
cells from apoptosis via a mechanism that is independent of CD106
(vascular cell adhesion molecule-1). The interaction between CLL cells
and NLCs may represent a novel target for therapy of patients with this disease.
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