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a Department of Pediatric Hematology and Oncology, Medical School Hannover, 30625 Hannover, Germany
Key Words: LEF-1 • severe congenital neutropenia • ELA2 • HAX1 • C/EBP- 
Address for correspondence: Dr. Karl Welte, Department of Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Voice: +49-511-532-6710; fax: +49-511-532-9120. Welte.Karl.H{at}mh-hannover.de
We found that lymphoid enhancer-binding factor 1 (LEF-1) is a decisive transcription factor in granulopoiesis controlling proliferation, proper lineage commitment, and granulocytic differentiation via regulation of its target genes C/EBP-
, cyclin D1, c-myc, and survivin. Myeloid progenitor cells of patients with severe congenital neutropenia (CN) showed a severe downregulation of LEF-1 and its target genes expression. Expression of neutrophil elastase (NE) is also severely reduced in CN myeloid progenitors. Intriguingly, ELA2 gene promoter is positively regulated by direct binding of LEF-1 or LEF-1 target gene C/EBP-. In summary we demonstrated that LEF-1 is not only crucial in lymphopoiesis, but also in myelopoiesis, documenting new functions of LEF-1.
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