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Gene Linked to Worse Childhood Leukemia Prognosis

Gene regulates B-cell development

WEDNESDAY, Jan. 7 (HealthDay News) -- Deletions in a gene regulating B-cell development are associated with a worse prognosis in children with high-risk B-cell-progenitor acute lymphoblastic leukemia (ALL), according to a report published online Jan. 7 in the New England Journal of Medicine.

Charles G. Mullighan, M.D., from St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues assessed abnormalities in DNA copy number in 221 children with high-risk B-cell-progenitor ALL, excluding known very high-risk subtypes, and their association with prognosis.

The researchers identified more than 50 recurring copy-number abnormalities, where 66.8 percent involved genes encoding regulators of B-cell development. Copy-number abnormalities in the IKZF1 gene were present in 28.6 percent of patients, the investigators found. A predictor of poor outcome was associated with alterations in IKZF1, which encodes a lymphoid transcription factor, in these patients as well as an independent group of 258 children with B-cell-progenitor ALL. The gene expression signature was similar to that of BCR-ABL1-positive ALL, a high-risk ALL type that has also often lost the IKZF1 gene, the report indicates.

"In summary, we identified an association between alterations of IKZF1 and the clinical outcome in B-cell-progenitor ALL in childhood," Mullighan and colleagues write. "Integrated genomic analysis suggests that IKZF1 contributes directly to treatment resistance in ALL."

Several study authors disclosed financial relationships with the pharmaceutical industry.

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