( called master genes that control the ...)Major gene study uncovers secrets of leukemia

The researchers found that the "PAX5" gene was most frequently mutated—altered in about 30 percent of patients. These mutations reduced the level of PAX5 protein in leukemic cells or resulted in the formation of PAX5 protein with defective function. Mutations were also found in other genes with important roles in B-cell differentiation including "EBF1" and "Ikaros."

"Although the identification of such a high frequency of mutations in this pathway was surprising, it is important to note that the approach used provides a lower limit of the true frequency of these mutations, since not every gene in this pathway could be accurately analyzed using this methodology," Downing said.

The mutations identified in "PAX5," "EBF" and "Ikaros" are likely to directly contribute to this block in normal lymphocyte differentiation, according to Downing. These genes encode proteins called transcription factors, which orchestrate the expression of a large number of other genes involved in B cell development. Together these genes coordinate the complex changes needed to induce progenitor cells to differentiate into B lymphocytes. In ALL, the leukemic cells fail to differentiate normally and instead remain blocked at an immature stage of development. Locked in this state, the leukemic cells continue to proliferate, and this continual growth of leukemic cells eventually kills the child.

"The new insights into the differentiation of B cells are extremely valuable," said Ching-Hon Pui, M.D., chair of the Oncology department and American Cancer Society Professor at St. Jude. Pui co-authored the paper. "The more we learn about why progenitor cells get stuck in the primitive, cancerous stage, the more likely we'll be able to design new therapies that eliminate them. That could help us continue our successful efforts to increase the su
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Source:St. Jude Children's Research Hospital