DELETIONS OF THE SHORT ARM OF CHROMOSOME-9, INCLUDING THE INTERFERON-ALPHA -BETA GENES, IN ACUTE LYMPHOCYTIC-LEUKEMIA - STUDIES ON LOSS OF HETEROZYGOSITY, PARENTAL ORIGIN OF DELETED GENES AND PROGNOSIS/

A restriction fragment length polymorphism (RFLP) analysis of the alph a- and beta-interferon (IFN) genes was performed in malignant cells fr om 52 patients with acute lymphocytic leukemia (ALL). Normal cell DNA was available for comparison in 23 of the patients. Ten patients were found to have gross alterations of their alpha- and beta-IFN genes. Le ukemic cells from 2 ALL patients showed a complete loss of alpha- and beta-IFN genes. Seven patients had a hemizygous loss of one of the alp ha- and beta-IFN alleles, as shown by RFLP analysis and/or loss of sig nal intensity. In one other patient the malignant clone was reduced to homozygosity with regard to the alpha- and beta-IFN genes, without lo ss of signal intensity. In patients without hemizygous deletions, the overall incidence of complete homozygosity for the alpha- and beta pol ymorphisms was higher than expected. Analysis of the data indicates th at the total frequency of ALL clones with gross alterations of the IFN -loci is around 30%. A 9p24 probe detected hemizygous deletions in 2 c ases of IFN gene deletions. In the other tested cases the deletions we re interstitial. No deletions of 9p24 were detected in patients withou t allelic losses of IFN genes. In 5 cases of allelic IFN gene deletion s, DNA from parents was available for comparison. In 4 cases the delet ed allele was derived from the mother, whereas in the fifth it origina ted from the father. Pediatric ALL patients with IFN-gene deletions or homozygosity for all polymorphisms in the IFN-loci had a significantl y worse prognosis than heterozygotes. We conclude that deletion of alp ha- and beta-IFN genes is a relatively common event in ALL and that RF LP analysis of the IFN genes may provide additional prognostic informa tion in childhood ALL. Whether or not the IFNs act as tumor-suppressor genes in this disease is not yet known. (C) 1993 Wiley-Liss, Inc.