March 6, 2012

Red Blood Cell Growth Linked to Leukemia?

(Ivanhoe Newswire)-- Yale researchers have discovered how megakaryocytes or giant blood cells that produce wound healing platelets grow 10 or more times bigger than other blood cells and how they may cause a form of leukemia.

"A failure of these cells to grow might be an initial trigger for megakaryoblastic leukemias," Diane Krause, senior researcher for the Yale Cancer Center, professor of laboratory medicine, cell biology, and pathology and associate director of the Yale Stem Cell Center, was quoted as saying.

Megakaryocytes grow so large because the DNA within the cell duplicates over and over again – but without the cell undergoing cell division. A megakaryoblastic can house more than 120 sets of nuclear DNA before it becomes the biological equivalent of a supernova, undergoing significant changes to break apart into thousands of platelets needed for normal blood clotting.

A Yale team led by postdoctoral associate Yuan Gao discovered that two proteins called guanine exchange factors (GEF-H1) halt endomitosis. They found that without GEF-H1, nuclear DNA couldn't go from two internal nuclei to four. Additional divisions of nuclear DNA within the cell could not occur unless there was reduced expression of ECT2.

The team was intrigued by the results because a gene implicated in malignant leukemias, MKL1, also seems to be necessary to promote normal megakaryocyte maturation. The Krause lab is now studying whether mutant forms of MKL1 may keep levels of GEF-H1 high, therefore, making it impossible for megakaryocytes to undergo endomitosis and building the foundation for development of cancer.

"These findings reveal another important step toward the formation of functional platelets, which are necessary for normal blood clotting," Krause said. "But they also provide a clue regarding what may go away to transform normal megakaryocytes into malignant leukemia cells."

SOURCE: Developmental Cell, March 2012.