Juvenile Myelomonocytic Leukemia (JMML) Cells Spontaneously Differentiate into Dendritic-cell Like Populations

Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/ myeloproliferative malignancy of early childhood, characterized by monocytosis, hepatos­plenomegaly and an aggressive clinical course. In semi-solid culture JMML progenitor cells proliferate spontaneously into colony forming units. In order to study the mechanisms of proliferation and differentiation of JMML cells we developed a suspension culture system without additional exogenous growth factor supplement. Mononuclear cells (MNC) from peripheral blood, bone marrow or spleen of 14 patients with JMML and 24 controls were studied. JMML cells expressed higher levels of the proliferation marker Ki67 (median 24% [7-39%] vs a median of 3.5% in controls). 90% of JMML cells were CD68-positive (vs 35% in controls) and by day 7 all JMML samples contained CD1a- positive cells. Electron microscopy demonstrated cytoplasmic vesicular structures resembling multilamellar MHC II compare­timents, which together with the expression of CD1a - support a dendritic cell (DC)-phenotype. Differentiation into CD1a-positive DC seems to be a frequent phenomenon in cultured JMML MNC, which in vivo may contribute to clinical characteristics such as skin and organ infiltration