Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1993-06-17
1996-01-30
Parr, Margaret
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
536 242, 536 243, 536 2431, 536 235, C12Q 168
Patent
active
054879701
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 BamHI 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:
Cimino, G. et al., "Cloning of ALL-1, the Locus Involved in Leukemias with the t(4;11) (q21;q23), t(9;11) (p22;q23), and t(11;19) (q23;p13) Chromosome Translocations," Cancer Research, 51:6712-6714, 1991.
Cimino, G. et al., "An Altered 11-Kilobase Transcript in Leukemic Cell Lines with the 4(4;11) (q21;q23) Chromosome Translocation," Cancer Research, 52:3811-3813, 1992.
Djabali, Malek et al., "A Trithorax-Like Gene is Interrupted by Chromosome 11q23 Translocations in Acute Leukemias," Nature Genetics, 2:113-118, 1992.
Gu, Y. et al., "The t(4;11) Chromosome Translocation of Human Acute Leukemias Fuses the ALL-1 Gene, Related to Drosophila Trithorax, to the AF-4 Gene" Cell, 71:701-708, 1992.
Gu, Y. et al., "The (4;11) (q21;q23) Chromosome Translocations in Acute Leukemias Involve the VDJ Recombinase," Proc. Natl. Acad. Sci. USA, 89:10464-10468, 1992.
Rowley, Janet D. et al., "Mapping Chromosome Band 11q23 in Human Acute Leukemia with Biotinylated Probes: Identification of 11q23 Translocation Breakpoints with a Yeast Artificial Chromosome," Proc. Natl. Acad. Sci. USA, 87, 9358-9362, 1990.
Tkachuk, Douglas C. et al., "Involvement of a Homolog of Drosophila Trithorax by 11q23 Chromosomal Translocations in Acute Leukemias," Cell, 71:691-700, 1992.
Ziemin-Van Der Poel, Sheryl et al., "Identification of a Gene, MLL, that Spans the Breakpoint in 11q23 Translocations Associated with Human Leukemias," Proc. Natl. Acad. Sci. USA, 88:10735-10739, 1991.
1988 Stratagene Catalog, p. 39.
Diaz Manuel O.
Rowley Janet D.
Arch Development Corp.
Houtteman Scott William
Parr Margaret
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