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Dendritic cells in chronic myelomonocytic leukaemia
Author(s) -
Vuckovic S.,
Fearnley D. B.,
Gunningham S.,
Spearing R. L.,
Patton W. N.,
Hart D. N. J.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01431.x
Subject(s) - cd14 , monocyte , dendritic cell , bone marrow , chronic myelomonocytic leukemia , cd80 , immunology , cd86 , cd16 , medicine , myeloid , biology , antigen , flow cytometry , immune system , in vitro , cd40 , t cell , cytotoxic t cell , myelodysplastic syndromes , biochemistry , cd3 , cd8
Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14 + monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age‐matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non‐significant) reduction from 9.8 × 10 6 /l in normal individuals to 7.5 × 10 6 /l in CMML patients. The CD14 low CD16 + monocyte subpopulation was not found in CMML patients. After culture in GM‐CSF/IL‐4, CMML CD14 + monocytes acquired the phenotype of immature monocyte derived DC (Mo‐DC) with similar yields to normal blood Mo‐DC generation. Addition of TNF‐α or LPS induced both normal and CMML Mo‐DC to express prominent dendritic processes, the CMRF44 + and CD83 + antigens and high levels of HLA‐DR, CD80 and CD86. Treatment either with TNF‐α or LPS increased the allostimulatory activity of normal Mo‐DC, but had little effect on the allostimulatory activity of CMML Mo‐DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.