April 11, 2013

Leukemia culprit’s cellular actions

Overexpression of a gene that is a common culprit in leukemia induces stem cell-like features in T cells, which may enable the cells to become cancerous.

Photomicrograph of acute lymphoblastic leukemia cells. (Wellcome Images)

The Lmo2 (LIM domain only 2) protein, which has a role in maintaining hematopoietic – blood-forming – stem cells, is one of the most frequently deregulated oncogenes in human acute T-cell lymphoblastic leukemia (T-ALL). It is unclear how overexpression of Lmo2 transforms T cells into leukemic cells.

In previous studies, Utpal Davé, M.D., assistant professor of Medicine, and colleagues found that forced overexpression of Lmo2 in multiple types of hematopoietic cells leads to leukemia only in T cells. They have now analyzed the proliferation, differentiation (maturation to specialized cell types) and cell death in T-cell progenitors from a transgenic mouse model that overexpresses Lmo2 in these cells.

They report in the journal Stem Cells that T-cell progenitors overexpressing Lmo2 have stem cell-like features: they are blocked in differentiation, quiescent and can replicate indefinitely (were immortalized) in vitro. The cells also had a transcriptional signature (set of expressed genes) that matched hematopoietic stem cells.

The findings have implications for understanding and treating Lmo2-induced leukemia.

This research was supported by the National Institutes of Health (HL089403), the Leukemia & Lymphoma Society, the Vanderbilt-Ingram Cancer Center, a Monforton family grant and the T.J. Martell Foundation.