Title:
METHOD OF INDUCING APOPTOSIS IN LYMPHOID CELLS
Document Type and Number:
WIPO Patent Application WO2002024866
Kind Code:
A3
Abstract:
A two-stage, transcriptionally regulated apoptotic program has been discovered. In the first stage, IL-3 withdrawal results in transcriptional activation of the NGAL gene followed by synthesis and secretion of NGAL protein. In the second stage, secreted NGAL protein induces apoptosis in lymphoid cells by an autocrine mechanism. Based on this discovery, the invention provides a method of inducing apoptosis in a lymphoid cell in a mammal, e.g., a human patient. The invention includes administering a therapeutically effective amount of an NGAL polypeptide or NGAL-like polypeptide to a mammal.
Inventors:
GREEN MICHAEL R (US)
DEVIREDDY LAXMINARAYANA (US)
TEODORO JOSE G (US)
RICHARD FABIAN (US)
DEVIREDDY LAXMINARAYANA (US)
TEODORO JOSE G (US)
RICHARD FABIAN (US)
Application Number:
PCT/US2001/029513
Publication Date:
October 03, 2002
Filing Date:
September 21, 2001
Export Citation:
Assignee:
UNIV MASSACHUSETTS (US)
GREEN MICHAEL R (US)
DEVIREDDY LAXMINARAYANA (US)
TEODORO JOSE G (US)
RICHARD FABIAN (US)
GREEN MICHAEL R (US)
DEVIREDDY LAXMINARAYANA (US)
TEODORO JOSE G (US)
RICHARD FABIAN (US)
International Classes:
A61K38/17; A61K38/57; (IPC1-7): C07K14/00; C12N15/85; C12N15/86
Other References:
COWLAND J.B. ET AL.: "Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans", GENOMICS, vol. 45, 1997, pages 17 - 23, XP002909708
FRIEDL A. ET AL.: "Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues cell type-specific patterns of expression", HISTOCHEMICAL JOURNAL, vol. 31, no. 7, 1999, pages 433 - 441, XP002909707
NIELSEN B.S. ET AL.: "Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel disease", GUT, vol. 38, no. 3, 1996, pages 414 - 420, XP002909706
BUNDGAARD J.R. ET AL.: "Molecular cloning and expression of a cDNA encoding NGAL: A lipocalin expressed in human neutrophils", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 202, no. 3, 15 August 1994 (1994-08-15), pages 1468 - 1475, XP002036694
FRIEDL A. ET AL.: "Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues cell type-specific patterns of expression", HISTOCHEMICAL JOURNAL, vol. 31, no. 7, 1999, pages 433 - 441, XP002909707
NIELSEN B.S. ET AL.: "Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel disease", GUT, vol. 38, no. 3, 1996, pages 414 - 420, XP002909706
BUNDGAARD J.R. ET AL.: "Molecular cloning and expression of a cDNA encoding NGAL: A lipocalin expressed in human neutrophils", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 202, no. 3, 15 August 1994 (1994-08-15), pages 1468 - 1475, XP002036694
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