James Mark Downing

US Patent:

20040018513, Jan 29, 2004

Filed:

Mar 18, 2003

Appl. No.:

10/391271

Inventors:

James Downing - Cordova TN, US
Eng-Juh Yeoh - Singapore, SG
Dawn Wilkins - Oxford MS, US
Limsoon Wong - Singapore, SG

International Classification:

C12Q001/68

US Classification:

435/006000

Abstract:

The present invention provides methods and compositions useful for diagnosing and choosing treatment for leukemia patients. The claimed methods include methods of assigning a subject affected by leukemia to a leukemia risk group, methods of predicting whether a subject affected by leukemia has an increased risk of relapse, methods of predicting whether a subject affected by leukemia has an increased risk of developing secondary acute myeloid leukemia, methods to aid in the determination of a prognosis for a subject affected by leukemia, methods of choosing a therapy for a subject affected by leukemia, and methods of monitoring the disease state in a subject undergoing one or more therapies for leukemia. The claimed compositions include arrays having capture probes for the differentially-expressed genes of the invention, computer readable media having digitally-encoded expression profiles associated with leukemia risk groups, and kits for diagnosing and choosing therapy for leukemia patients.

US Patent:

20100240057, Sep 23, 2010

Filed:

Nov 6, 2008

Appl. No.:

12/738759

Inventors:

James Downing - Memphis TN, US
Charles Mullighan - Memphis TN, US

Assignee:

St. Jude Children's Research Hospital - Memphis TN

International Classification:

C12Q 1/68

US Classification:

435 6

Abstract:

Compositions and methods for the identification, prognosis, classification, treatment, and diagnosis of leukemia or a genetic predisposition to leukemia are provided. The present invention is based on the discovery of various genomic abnormalities of the IKZFl gene which are shown herein to be associated with acute lymphoblastic leukemia (ALL), more particularly, associated with BCR-ABL1 positive ALL and/or shown to be associated with chronic myeloid leukemia (CML), more particularly, associated with blast crisis chronic myeloid leukemia (BC-CML) and/or the likelihood of progression into blastic transformation of CML. These various genomic abnormalities of the IKZFl gene can further be used as prognostic markers to identify a subgroup of ALL having very poor outcomes. Such genomic abnormalities of IKZFl find use in methods and compositions useful in the identification and/or prognosis and/or predisposition and/or treatment of ALL, more particularly, BCR-ABL1 positive ALL and/or in the identification and/or prognosis and/or predisposition and/or treatment of CML, more particularly, of BC-CML and/or the likelihood of progression into blastic transformation of CML and/or as prognostic markers to identify a subgroup of ALL having very poor outcomes.

US Patent:

20110047634, Feb 24, 2011

Filed:

Feb 4, 2009

Appl. No.:

12/866511

Inventors:

James Downing - Memphis TN, US
Charles Mullighan - Memphis TN, US

International Classification:

A01K 67/00
C07H 21/04
C07K 14/47
C12Q 1/68
C07H 21/00
C40B 30/04
G01N 33/68
G01N 33/566

US Classification:

800 13, 536 235, 530350, 435 6, 536 2431, 506 9, 436 86, 435 71, 435 721

Abstract:

Compositions and methods for the identification, prognosis, classification, diagnosis, and treatment of leukemia or a genetic predisposition to leukemia are provided. The present invention is based on the discovery of a novel intragenic deletion in the v-ets erythroblastosis virus E26 oncogene homolog (ERG) allele which is shown herein to be associated with a novel subtype of B-progenitor acute lymphoblastic leukemia (ALL). In one embodiment, the intragenic deletion in ERG results in the expression of C-terminal domain deletion forms of the ERG polypeptide which lacks the DNA-binding PNT domain and CAE domain of the ERG polypeptide and have dominant negative ERG activity. In other embodiments, the intragenic deletions results in a loss of expression of the native ERG polypeptide. Such nucleotide sequences and amino acid sequences of ERG find use in methods and compositions useful in the identification and/or the prognosis and/or predisposition and/or treatment of ALL, more particularly, the novel subtype of B-progenitor AL.

US Patent:

60338474, Mar 7, 2000

Filed:

Feb 6, 1995

Appl. No.:

8/384106

Inventors:

Charles J. Sherr - Memphis TN
James Downing - Cordova TN
Hiroshi Hirai - Memphis TN
Tsukasa Okuda - Memphis TN

Assignee:

St. Jude Children's Research Hospital - Memphis TN

International Classification:

C12Q 168
C07H 2100
C12N 1512
C12N 1585
C07K 14435

US Classification:

435 6

Abstract:

Members of the InK4 (Inhibitors of CDK4) family inhibit the activities of specific cyclin D-dependent kinases (CDK4 and/or CDK6), thereby arresting cell cycle progression in G1 phase and preventing chromosomal DNA replication. Disclosed herein are novel mammalian InK4 family members, having apparent molecular masses of 18,000 and 19,000 daltons, designated "InK4c-p18" and "InK4d-p19," respectively, or simply "p18" and "p19. " In particular, the invention provides p19 genes and proteins isolated from murine or human cells and p18 genes and proteins from murine cells. When constitutively expressed in cells, p19 inhibits cyclin D-dependent kinase activity in vivo and induces G1 phase arrest. Materials and methods disclosed herein include (1) nucleic acids that encode p18 or p19; (2) methods for detecting nucleic acids encoding p18 or p19 proteins; (3) methods for producing p18 or p19 proteins using nucleic acids that encode p18 or p19, respectively; (4) purified pl8 or p19 proteins and peptide fragments, oligopeptides, or fusion proteins derived therefrom; (5) methods of inhibiting cells from replicating their chromosomal DNA using purified p18 or p19 proteins or derivatives thereof; (6) antibodies that specifically bind p18 or p19; (7) methods for detecting p18 and p19 proteins; (8) methods of stimulating cell growth by blocking p18 or p19 expression via antisense oligonucleotides; (9) methods of gene therapy using nucleic acids that encode p18 or p19; and (10) methods of making transgenic non-human animals that have alterations in the gene encoding p18 or p19, or in both genes.