The nuclear migration gene NudC and human hematopoiesis.

The filamentous fungus Aspergillus nidulans nudC (nuclear distribution C) gene is required for movement of nuclei following mitosis and for normal colony growth. It is highly conserved, structurally and functionally, throughout most of evolution. The human homolog, called HnudC, has been cloned and has an important role in cell proliferation. In hematopoiesis, HNUDC is highly expressed in early hematopoietic precursors and declines during normal differentiation. Stimulation of proliferation of the erythroleukemia cell line TF-1 with GM-CSF enhances HnudC protein and mRNA expression and treatment with antisense (but not sense) oligonucleotides to HnudC mRNA significantly reduces cell division. A significant increase in HNUDC is present in bone marrow aspirates from patients with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) compared to the level in normal cellular counterparts, demonstrating dysregulated expression in leukemia. These data support the conclusion that HnudC plays a functional role in promoting hematopoietic cell growth and that it is involved in leukemogenesis.