TEL AND KIP1 DEFINE THE SMALLEST REGION OF DELETIONS ON 12P13 IN HEMATOPOIETIC MALIGNANCIES

Unbalanced translocations as well as interstitial deletions of the sho rt arm of chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. These chang es result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome containing the TEL gene, a cosmid contig containing part of TEL and a pi contig containing the KIP1 gen e to 12p13. These probes were used for fluorescence in situ hybridizat ion to analyze samples from 47 patients with various hematologic malig nancies who had unbalanced translocations (25 patients) leading to los s of 12p or deletions (22 patients) involving 12p13. The patients had acute lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy-related MDS or AML (7 cases), non-Hodgki n's lymphoma (2 cases), and other hematopoietic malignancies (5 cases) . All three probes were hemizygously deleted in 26 cases and were comp letely retained in only 9 cases. In 12 cases probes for one of the two genes were deleted, allowing us to map the smallest region of overlap of these deletions to a small genomic region that is bordered on the telomeric side by the TEL gene and on the centromeric side by KIP1. Th e genomic distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp. (C) 1995 by The American Society of Hematology.