Commitment of juvenile myelo-monocytic (JMML) leukemic cells to spontaneously differentiate into dendritic cells

Abstract

Juvenile myelo-monocytic leukemia (JMML) is a severe malignant stem cell disorder of childhood. A proportion of cells from JMML mononuclear cells (MNC) spontaneously differentiate in vitro into dendritic cells (DC). We have studied MNC from 14 JMML patients, and characterized their functional activity as antigen presenting cells (APC). Large cells, differentiated after seven days of culture, expressed high levels of MHC II molecules and Mannose Receptor, variable levels of CD80 and CD86, and low levels of CD1a. Similar to immature DC, cells from JMML had high levels of dextran endocytosis, and were able to elicit proliferation of allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD40L-matured DC from JMML was associated with relevant increase of CD80, CD86 and CD83, increased APC activity, responded in chemotaxis assays to MIP-3beta and secreted increased amounts of macrophage derived chemokine (MDC). Immature DC and CD40L-matured DC from JMML produced very low amounts of IL-12, whereas the production of IL-10 was higher than normal DC. In line with these findings, they showed defective capacity to polarize naive T cells to differentiate into Th1 effectors. These results indicate that MNC from JMML are committed to spontaneously differentiate into DC with morphological and phenotypical characteristics similar to normal DC. The cytokine profile produced by these APC is likely to suppress and not to elicit a protective immune response.

CD1c(+) myeloid dendritic cells in myeloid neoplasia

“…CD1c(+) MDCs were increased in the three JMML patients evaluated in our study including one patient with 8% CD1c(+) MDCs. Interestingly JMML mononuclear cells have been noted to spontaneously differentiate into dendritic cells in vitro . The frequent increase in CD1c(+) MDCs in JMML and CMML suggest that myelomonocytic malignancies may demonstrate significant CD1c(+) MDC differentiation.…”

CD4+/CD56+ Hematodermic Tumor

“…51,105 The induction of phenotypic and functional properties of monocytic DCs in vivo has also been described for tumor cells derived from AML and juvenile myelomonocytic leukemia. 112,113 Horny et al 114 reported a case that progressed from MDS to CMML with marked lymphotropism and atypical clusters of pDC-differentiated cells.…”

Generation of immunostimulatory dendritic cells from the malignant clone in patients with juvenile myelomonocytic leukemia

“…Longoni et al 8 have recently shown that JMML cells can spontaneously differentiate in vitro into DC, but these leukemic DC secrete the immunosuppressive cytokine IL-10 that might dampen autologous antileukemia responses. However, we have found that adherent JMML cells cultured in vitro with GM-CSF and IL-4 differentiate into stimulatory DC capable of inducing allogeneic antileukemia immune responses.…”