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New chromosomal abnormality identified in leukemia associated with Down syndrome
Date:10/18/2009

he uncontrolled cell growth that is a hallmark of cancer.

JAK mutations have also been linked to other cancers. Drugs targeting JAK kinases are already in clinical trials against a variety of blood disorders in adults. Additional trials are being planned against other subtypes of childhood ALL.

In this study, researchers reported a significant association between alterations in both the CRFL2 and JAK2 genes. Almost all JAK mutations were observed in patients with CRLF2 alterations. Almost 28 percent of children with Down syndrome and ALL had changes in both the CRFL2 and JAK genes.

"It has been a mystery as to why the JAK mutations in Down syndrome ALL are different from those seen in other cancers," Mullighan said. "Here we show that the JAK mutations in ALL are almost always observed together with a chromosomal alteration that results in over- expression of CRLF2."

When both the JAK mutation and increased CRLF2 production were introduced into white blood cells growing in the laboratory, those cells were transformed and no longer needed cytokines to grow. Neither genetic alteration on its own produced the same effect. Researchers also reported their impact could be weakened by the addition of drugs that target JAK mutations.

"We showed that the two proteins, CRLF2 and mutant JAK2, physically interact, and together transform white blood cells. This work has identified a new pathway contributing to the development of leukemia," Mullighan said. A next step is to determine if these mutations also interact in mouse models of ALL.


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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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