New Chromosomal Abnormality Identified in Leukemia Associated with Dow...(s commonly associated with childhood ALL...),Health

The new gene alteration was identified by St. Jude scientists following up on an earlier observation. They had previously found a recurring deletion in a region of DNA duplicated on the X and Y chromosomes. The region is known as pseudoautosomal region 1 or PAR1.

The PAR1 deletion was found only in patients with a subtype of ALL known as B-progenitor ALL. It was most common in children with both B-progenitor ALL and Down syndrome. In this study, investigators screened almost 400 children with ALL, including 75 patients with Down syndrome. The deletion was present in 7 percent of patients with B-progenitor ALL, but in more than half of the patients with both B progenitor and Down syndrome.

The deletion results in a fusion of two genes, P2RY8 and CRLF2. The fusion puts CRLF2 expression under the control of the P2RY8 promoter. As a result, CRLF2 expression jumps as much as 10 fold.

"CRLF2 over-expression identifies a group of ALL cases which were not previously well characterized, and suggests some novel treatment approaches that may improve patient survival. Patients with Down syndrome are particularly vulnerable to complications from standard chemotherapy, and could therefore benefit from novel therapies," said Karen Rabin, M.D., of Texas Children's Cancer Center and a study co-author. She is a Baylor College of Medicine assistant professor of pediatric hematology/oncology.

The CRLF2 protein normally forms part of a receptor where a small growth factor known as a cytokine binds to white blood cells known as lymphocytes. Both the cytokine, thymic stromal lymphopoietin (TSLP), and CRLF2 are known to play important roles in the development of immune cells known as T lymphocytes as well as in inflammation and allergic disease. They had not previo
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