Pathogenic Mechanisms in Juvenile Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia (JMML) is a relentless myeloproliferative disorder (MPD) of young children characterized by over-production of myeloid lineage cells that infiltrate hematopoietic and non-hematopoietic tissues including skin, lung, and spleen. The median survival is < 1 year without hematopoietic stem cell transplantation (HSCT). A cellular hallmark of JMML is that primary blood or bone marrow cells form abnormal numbers of colony forming unit granulocyte-macrophage (CFU-GM) colonies in methylcellulose cultures containing low concentrations of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Children wit