Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes.
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.
Pellagatti
Andrea
A
LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK.
Marafioti
Teresa
T
Paterson
Jennifer C
JC
Malcovati
Luca
L
Della Porta
Matteo G
MG
Jädersten
Martin
M
Pushkaran
Beena
B
George
Tracy I
TI
Arber
Daniel A
DA
Killick
Sally
S
Giagounidis
Aristoteles
A
Hellström-Lindberg
Eva
E
Cazzola
Mario
M
Wainscoat
James S
JS
Boultwood
Jacqueline
J
D018952:Antigens, CD34 / Q000032:analysis; D016022:Case-Control Studies; D018450:Disease Progression; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000032:analysis / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009503:Neutropenia; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018952:Antigens, CD34; D051821:Lymphoid Enhancer-Binding Factor 1; D012333:RNA, Messenger