Dendritic cells in chronic myelomonocytic leukaemia

Blood dendritic cells (DC) differentiate ill vitro via two separate pathway s: either directly from blood DC precursors (DCp) or from CD14(+) monocytes . In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursor s 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 blo od monocytes was accompanied by a reciprocal decrease in mean blood DC perc entage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML pat ients). Absolute blood DC numbers showed a minimal (non-significant) reduct ion from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patie nts. The CD14(low)CD16(+) monocyte subpopulation was not found in. CMML pat ients. After culture in GM-CSF/IL-4. CMML CD14(+) monocytes acquired the ph enotype of immature monocyte derived DC (Mo-DC) with similar yields to norm al blood Mo-DC generation, Addition of TNF-alpha 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 eithe r with TNF-a or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perha ps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, sugge sting discrete regulation of monocyte and DC production.