Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes.
Pellagatti A., Marafioti T., Paterson JC., Malcovati L., Della Porta MG., Jädersten M., Pushkaran B., George TI., Arber DA., Killick S., Giagounidis A., Hellström-Lindberg E., Cazzola M., Wainscoat JS., Boultwood J.
Lymphoid enhancer-binding factor 1 (LEF1) is a neutrophilic granulopoiesis regulator whose absence is critical in congenital neutropenia. We have shown LEF1 downregulation in the CD34(+) cells of the majority of myelodysplastic syndromes (MDS) patients. LEF1 was the most significant differentially expressed gene between early and advanced MDS. Marked LEF1 downregulation was found in 27/32 patients with advanced MDS and in 6/35 patients with early MDS, and was associated with neutropenia. Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS.