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Researchers Identify New Gene That Predisposes People to ALL

Laura Joszt
Researchers have identified a new gene that may predispose individuals to develop acute lymphoblastic leukemia (ALL). In addition, variants in the gene can influence patient response to treatment.
Researchers have identified a fourth gene that may predispose individuals to develop acute lymphoblastic leukemia (ALL), according to a study published in Cancer Cell. The gene IKZF1 joins 4 other genes—TP53, ETV6, and PAX5—which have been identified as predisposing carriers to develop B-cell ALL.

In addition to IKZF1 indicating individuals who have an increased susceptibility to ALL, variants in the gene can influence patient response to treatment.

"This finding adds to the growing body of evidence that, while germline variations still account for a small percentage of pediatric ALL cases overall, more children than previously recognized inherit a predisposition to develop ALL," Charles Mullighan, MBBS, MD, a member of the St. Jude Department of Pathology, said in a statement.

A decade ago, Mullighan and colleagues first reported that IKZF1 was often mutated in leukemic cells and were an indication that the individual would have poor treatment outcomes.

While not everyone carrying a germline IKZF1 variant will develop ALL, the findings mean families can be informed about the potential risk to develop leukemia, added co-author Kim Nichols, MD, director of the St. Jude Cancer Predisposition Division.

The history of research into IKZF1 included 3 generations of a German family with a germline variation of the gene and a family history of B-cell ALL. Researchers found that 2 of the 5 family members with the variant developed ALL as children and died.

"In IKZF1 and the other ALL predisposition genes, cells may require an additional cooperating mutation to develop into leukemia," Mullighan said. "While familial ALL is rare, these cases can point to genes and novel biology to examine in a larger patient population.

Reference

Churchman ML, Qian M, Kronnie G et al. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. [published online April 19, 2018]. Cancer Cell. doi: 10.1158/2159-8290.CD-RW2018-073.

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