Mutation Linked to Leukemia in Down Syndrome

September 22, 2008

About a fifth of Down syndrome patients with acute lymphoblastic leukemia have a mutation in the Janus kinase 2 (JAK2) protein, according to a report published online Sept. 20 in The Lancet.

MONDAY, Sept. 22 (HealthDay News) -- About a fifth of Down syndrome patients with acute lymphoblastic leukemia have a mutation in the Janus kinase 2 (JAK2) protein, according to a report published online Sept. 20 in The Lancet.

Dani Bercovich, Ph.D., from Tel-Hai Academic College in Israel, and colleagues analyzed JAK2 DNA mutations in bone marrow from 88 patients with Down syndrome-associated acute lymphoblastic leukemia, and 216 patients with sporadic acute lymphoblastic leukemia, Down syndrome-associated acute megakaryoblastic leukemia and essential thrombocythemia.

The researchers found that 18 percent of patients with Down syndrome-associated acute lymphoblastic leukemia had a JAK2 mutation; the one non-Down syndrome-associated leukemia patient with a mutation had an isochromosome 21q. The mean age of children with the mutant protein at diagnosis was significantly younger (4.5 versus 8.6 years), the investigators found. The five identified mutations all led to a change in a conserved arginine residue (R683). The mutant protein immortalized mouse cells and led to unregulated growth, the report indicates.

"Somatically acquired R683 JAK2 mutations define a distinct acute lymphoblastic leukemia subgroup that is uniquely associated with trisomy 21," Bercovich and colleagues conclude. "JAK2 inhibitors could be useful for treatment of this leukemia."

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