Compositions and methods for treating acute myeloid leukemia

Patent metadata

Field	Value
Publication number	US-2020323898-A1
Application number	US-201816767280-A
Country	US
Kind code	A1
Filing date	Nov 27, 2018
Priority date	Nov 28, 2017
Publication date	Oct 15, 2020
Grant date	—

Abstract

The present disclosure relates generally to methods for ameliorating or treating acute myeloid leukemia (AML). In particular, the present technology relates to administering a therapeutically effective amount of one or more compositions that inhibit the vitamin B6 pathway to a subject diagnosed with, or at risk for AML.

First claim

1 . A method for treating or preventing AML in a subject in need thereof, comprising administering to the subject
a therapeutically effective amount of at least one inhibitor of Vitamin B6 pathway selected from the group consisting of isoniazid, aftin-4, DFMO, gingkotoxin, aminooxyacetic acid, and myriocin, or a therapeutically effective amount of at least one sgRNA or shRNA that targets one or more genes selected from the group consisting of PDXK, PNPO, AZIN1, ODC1, GOT2, ALAS1, SPTLC1, and SPTLC2.

2 . (canceled)

3 . The method of claim 1 wherein the at least one sgRNA or shRNA comprises a nucleic acid sequence selected from the group consisting of:

(SEQ ID NO: 1)

5′ TGGCTACGTGGGTAACAGAG 3′ (Pdxk sg-1),

(SEQ ID NO: 2)

5′ ATCCAGAGCCATGTTGTCCG 3′ (Pdxk sg-2),

(SEQ ID NO: 3)

5′ GTGCAGTTTTCAAACCACAC 3′ (Pdxk sg-3),

(SEQ ID NO: 4)

5′ GCTTGGGGTGCCTGCAGAGA 3′ (Odc1-a106),

(SEQ ID NO: 5)

5′ TGCTGTTGACAGTGAGCGCCAAGGTGAACGATGTCAATAATAGT

GAAGCCACAGATGTATTATTGACATCGTTCACCTTGATGCCTACTGC

CTCGGA 3′ (Pdxk.307),

(SEQ ID NO: 6)

TGCTGTTGACAGTGAGCGCCAGGTTCAATGTGAGGTTACATAGTGAA

GCCACAGATGTATGTAACCTCACATTGAACCTGATGCCTACTGCCTC

GGA 3′ (Pdxk.3259),

(SEQ ID NO: 7)

5′ ACGCCCAGGATGGGATCTGG 3′ (Got2.a41),

(SEQ ID NO: 8)

5′ AAAGAATACCTGCCCATTGG 3′ (Got2.a99),

(SEQ ID NO: 9)

5′ GACTGGAGCCTTAAGGGTCG 3′ (Got2.a140),

(SEQ ID NO: 10)

5′ ATACAGAGCCACGTCATCCG 3′ (hPdxk-aa15),

(SEQ ID NO: 11)

5′ CGGCTACGTGGGCAACCGGG 3′ (hPdxk-aa22),

(SEQ ID NO: 12)

5′ GCCTACCGTACACCAGCCTG 3′ (hPdxk-aa105),

(SEQ ID NO: 13)

5′ GTCCCCAGTGCCCACAAAGA 3′ (hPDXK-aa230),

(SEQ ID NO: 14)

5′ AATGGCTTTAGTGCAAGAAT 3′ (Azin1-a100),

(SEQ ID NO: 15)

5′ GAACTACTCCGTTGGCCTGT 3′ (Azin1-a14),

(SEQ ID NO: 16)

5′ GCCAAGATCTCAAGCACGGC 3′ (Azin1-a76),

(SEQ ID NO: 17)

5′ ATATTGACGTCATTGGTGTG 3′ (Odc1-a194),

(SEQ ID NO: 18)

5′ AGGCAGCAGCGTCTTCCGCA 3′ (ALAS1 sg-1),

(SEQ ID NO: 19)

5′ CACCGTTTTAAAAACTCGGT 3′ (ALAS2 sg-2),

(SEQ ID NO: 20)

5′ CTCGGGATAAGAATGGGCAT 3′ (ALAS1 sg-3),

(SEQ ID NO: 21)

5′ TGCGTAAAAGGGAGTGACGC 3′ (Odc1-a62),

(SEQ ID NO: 22)

5′ GCTGGCCAACCCTCGAGTTA 3′ (SPTLC1 sg-1),

(SEQ ID NO: 23)

5′ GATGGTGCAGGCGCTGTACG 3′ (SPTLC1 sg-2),

(SEQ ID NO: 24)

5′ TCAACTACAACATCGTGTCC 3′ (SPTLC1 sg-3),

(SEQ ID NO: 25)

5′ GCTCCAGGCACACTACAGAT 3′ (SPTLC2 sg-1),

(SEQ ID NO: 26)

5′ GAACGGCTGCGTCAAGAACG 3′ (SPTLC2 sg-2),

(SEQ ID NO: 27)

5′ AATCTCGAAGATATCCAAAG 3′ (SPTLC2 sg-3),

(SEQ ID NO: 28)

5′ GGTGTGTGGTTTCCCCAGGT 3′ (hGOT2.a162),

(SEQ ID NO: 29)

5′ GATGGGTGTGTGGTTTCCCC 3′ (hGOT2.a163),

(SEQ ID NO: 30)

5′ GGACGCGGGTCCACTCCCGT 3′ (hGOT2.a218),

(SEQ ID NO: 31)

5′ TGGACCCGCGTCCGGAACAG 3′ (hGOT2.a224),

(SEQ ID NO: 39)

5′ ACGATGAACATGTTAGACAT 3′ (hAZIN1-a233),

(SEQ ID NO: 40)

5′ CTATGTTTATGAACATACCC 3′ (hAZIN1-a33),

(SEQ ID NO: 41)

5′ TATCTGCTTGATATTGGCGG 3′ (hODC1-a235),

(SEQ ID NO: 42)

5′ CAACGCTGGGTTGATTACGC 3′ (hODC1-a254),

(SEQ ID NO: 982)

5′ GGAGGTCCTGGGGAACGTAC 3′ (Pdxk sg-4),

(SEQ ID NO: 983)

5′ CATGGCAGCGAAGAGGTCCC 3′ (Pdxk sg-5),

(SEQ ID NO: 984)

5′ AGCTGTCTTCGTGGGCACCG 3′ (Pdxk sg-6),

(SEQ ID NO: 985)

5′ TGTAACCTCACATTGAACCTGA 3′,

(SEQ ID NO: 986)

Assignees

• Memorial Sloan Kettering Cancer Center
• Cold Spring Harbor Laboratory

Inventors

• Lowe Scott
• Zhang Lingbo
• Chen Chichao

Classifications

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• C12N15/11

  DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity} · CPC title

• C12N15/00

  Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor (mutants or genetically engineered microorganisms, per se C12N1/00, C12N5/00, C12N7/00; new plants per se A01H; plant reproduction by tissue culture techniques A01H4/00; new animals per se A01K67/00; use of medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases, gene therapy A61K48/00) · CPC title

• C12N15/09

  Recombinant DNA-technology · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title