Deficiency of CREB and over expression of miR-183 in juvenile myelomonocytic leukemia

Abstract

Juvenile myelomonocytic leukemia (JMML) is a rare leukemia of infancy and early childhood. A hallmark of JMML is that JMML cells are selectively hypersensitive to GM-CSF in vitro, but have normal sensitivity to IL-3, which shares the β-subunit receptor with GM-CSF.1, 2 The pathogenesis of JMML is linked to dysregulated signal transduction through the Ras signaling pathway caused by mutations of RAS, PTPN11 and c-CBL, or loss-of-heterozygosity of NF1.3, 4 Although most patients with JMML experience an aggressive disease course, some others spontaneously resolve.3, 5 No specific mutation has been definitively demonstrated to confer a poorer prognosis, with the exception of perhaps PTPN11, which has been shown to be associated with a higher risk of relapse in some series. In addition, gene expression and methylation analyses have identified signatures associated with outcome that are unexpectedly independent of genotype,5, 6 leading us to believe that additional mutations or events mitigate the course of JMML. Finally, the mechanisms that underlie selective GM-CSF hypersensitivity are not well established in JMML.