Open Access5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox
Author(s) -
Fabian Müller,
Tyler A. Cunningham,
Stephanie Stookey,
ChinHsien Tai,
Sandra Burkett,
Parthav Jailwala,
Maryalice Stetler Stevenson,
Margaret C. Cam,
Alan S. Wayne,
Ira Pastan
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1714512115
Subject(s) - leukemia , cancer research , cell culture , biology , bone marrow , pseudomonas exotoxin , immunotoxin , myeloid leukemia , microbiology and biotechnology , azacitidine , lymphoma , gene , immunology , gene expression , cytotoxicity , in vitro , genetics , recombinant dna , dna methylation
Significance Moxetumomab pasudotox is a fusion protein of an anti-CD22 Fv andPseudomonas exotoxin. It is highly active against leukemia in vitro but acute lymphoblastic leukemia (ALL) patients often are resistant. Studies with cultured cells showed resistance is caused by reduced diphthamide, the intracellular target ofPseudomonas exotoxin, but diphthamide is not reduced in most cells from most ALL patients. To study how resistance develops in animals, we injected ALL cells into mice and found that resistant cells occur in discrete bone marrow niches and contain major chromosomal and transcriptional changes. Mice pretreated with 5-azacytidine show greatly improved responses, supporting a trial of the combination in leukemia patients.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom