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

Objective: Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/ myeloproliferative malignancy of early childhood, characterized by monocytosis, hepatos-plenomegaly and an aggressive clinical course. Methods: 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. Findings: 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 compare-timents, which together with the expression of CD1a- support a dendritic cell (DC)-phenotype. Conclusion: 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