Compositions and methods for detecting gene rearrangements and t

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

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5303871, 5303881, 53038815, C07K 1400, C07K 1600, C07K 1618

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active

061214191

ABSTRACT:
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.

REFERENCES:
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Kobayashi et al., Heterogeneity of Breakpoints of 11q23 Rearrangements in Hematologic Malignancies Identified With Fluorescence In Situ Hybridization, Blood, 82(2):547-551, 1993.
Super et al., "Rearrangements of the MLL Gene in Therapy-Related Acute Myeloid Leukemia in Patients Previously Treated with Agents Targeting DNA-Topoisomerase II", Blood, 82(12):3705-3711, 1993.
Martinez-Climent et al., "Detection of 11q23/MLL Rearrangements in Infant Leukemias with Fluorescence In Situ Hybridization and Molecular Analysis", Leukemia 9:1299-1304, 1995.
Thirman et al., "Cloning of ELL, a Gene that Fuses to MLL in a t(11;19)(q23;p13.1)in Acute Myeloid Leukemia", Proc. Natl. Acad. Sci, USA, 91:12110-12114, 1994.
Thirman et al., "Rearrangement of the MLL Gene in Leukemia", Proc. Natl. Acad. Sci, USA, 329:909-914, 1993.
Zeleznik-Le et al., "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", Proc. Natl. Acad. Sci, USA, 91:10610-10614, 1994.

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