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Compositions and methods for detecting gene rearrangements and translocations

Patent ·
OSTI ID:873254
 [1];  [1]
  1. Chicago, IL
+ Show Author Affiliations
Disclosed is a series of nucleic acid probes for use in diagnosing and monitoring certain types of leukemia using, e.g., Southern and Northern blot analyses and fluorescence in situ hybridization (FISH). These probes detect rearrangements, such as translocations involving chromosome band 11q23 with other chromosomes bands, including 4q21, 6q27, 9p22, 19p13.3, in both dividing leukemic cells and interphase nuclei. The breakpoints in all such translocations are clustered within an 8.3 kb BamHI genomic region of the MLL gene. A novel 0.7 kb BamH1 cDNA fragment derived from this gene detects rearrangements on Southern blot analysis with a single BamHI restriction digest in all patients with the common 11q23 translocations and in patients with other 11q23 anomalies. Northern blot analyses are presented demonstrating that the MLL gene has multiple transcripts and that transcript size differentiates leukemic cells from normal cells. Also disclosed are MLL fusion proteins, MLL protein domains and anti-MLL antibodies.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL
DOE Contract Number:
FG02-86ER60408
Assignee:
Arch Development Corp. (Chicago, IL)
Patent Number(s):
US 6121419
OSTI ID:
873254
Country of Publication:
United States
Language:
English

References (6)

The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene journal November 1992
11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. journal October 1994
Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. journal December 1994
Rearrangement of the MLL Gene in Acute Lymphoblastic and Acute Myeloid Leukemias with 11q23 Chromosomal Translocations journal September 1993
The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. journal March 1990
Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA- topoisomerase II journal December 1993

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