Janus Kinase Mutations in Mice Lacking PU.1 and Spi-B Drive B Cell Leukemia through Reactive Oxygen Species-Induced DNA Damage-Reference-Cited by-同舟云学术

Janus Kinase Mutations in Mice Lacking PU.1 and Spi-B Drive B Cell Leukemia through Reactive Oxygen Species-Induced DNA Damage

Published:2020-08-28 Issue:18 Volume:40 Page:
ISSN:0270-7306
Container-title:Molecular and Cellular Biology
language:en
Short-container-title:Mol Cell Biol

Author:

Lim Michelle¹²,Batista Carolina R.¹²,de Oliveira Bruno R.¹,Creighton Rachel¹,Ferguson Jacob¹,Clemmer Kurt¹,Knight Devon¹,Iansavitchous James¹,Mahmood Danish¹,Avino Mariano³,DeKoter Rodney P.¹²⁴^ORCID

Affiliation:

1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

2. Division of Genetics and Development, Children’s Health Research Institute, Lawson Research Institute, London, Ontario, Canada

3. Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

4. Centre for Human Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

Abstract

Precursor B cell acute lymphoblastic leukemia (B-ALL) is caused by genetic lesions in developing B cells that function as drivers for the accumulation of additional mutations in an evolutionary selection process. We investigated secondary drivers of leukemogenesis in a mouse model of B-ALL driven by PU.1/Spi-B deletion (Mb1-CreΔPB). Whole-exome-sequencing analysis revealed recurrent mutations in Jak3 (encoding Janus kinase 3), Jak1 , and Ikzf3 (encoding Aiolos).

Funder

Gouvernement du Canada | Canadian Institutes of Health Research

Leukemia and Lymphoma Society of Canada

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Link

https://journals.asm.org/doi/pdf/10.1128/MCB.00189-20

Reference64 articles.

1. Genetic Basis of Acute Lymphoblastic Leukemia

2. Genomics in acute lymphoblastic leukaemia: insights and treatment implications