Myeloproliferation in mice lacking a lipoxygenase (KO) leads to bigger spleens.

Suppressing the action of lipoxygenases may reduce “bad cholesterol” deposition and inflammation in the arteries and thereby prevent heart attacks. But doing so might inadvertently cause leukemia, warn Middleton et al. (page 2529).

While studying atherosclerosis (artery hardening) using 12/15-lipoxygenase (12/15-LO) knock-out mice, Ellen Puré's team made an unexpected discovery: the spleens of all the mice were enlarged. Closer inspection of the spleens revealed a distinct increase in the myeloid cell population—a feature indicative of myeloid proliferative disease (MPD). Consistent with this leukemia, lymph nodes displayed an abnormal excess of cells, and the leukocyte count of peripheral blood was markedly increased.

12/15-LO−/− splenocytes showed increased levels of the Bcl-2 oncoprotein and reduced nuclear accumulation of the ICSBP transcription factor, which represses Bcl-2. Exactly how loss of 12/15-LO leads to loss of nuclear...

The Rockefeller University Press
2006
The Rockefeller University Press
2006
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