Journal article
Chromosomal instability upregulates interferon in acute myeloid leukemia
Genes chromosomes & cancer, Vol.59(11), pp.627-638
11/2020
DOI: 10.1002/gcc.22880
PMCID: PMC7597364
PMID: 32557940
Abstract
Chromosome instability (CIN) generates genetic and karyotypic diversity that is common in hematological malignancies. Low to moderate levels of CIN are well tolerated and can promote cancer proliferation. However, high levels of CIN are lethal. Thus, CIN may serve both as a prognostic factor to predict clinical outcome and as a predictive biomarker. A retrospective study was performed to evaluate CIN in acute myeloid leukemia (AML). Chromosome mis-segregation frequency was correlated with clinical outcome in bone marrow core biopsy specimens from 17 AML cases. Additionally, we induced chromosome segregation errors in AML cell lines with AZ3146, an inhibitor of the Mps1 mitotic checkpoint kinase, to quantify the phenotypic effects of high CIN. We observed a broad distribution of chromosome mis-segregation frequency in AML bone marrow core specimens. High CIN correlated with complex karyotype in AML, as expected, although there was no clear survival effect. In addition to CIN, experimentally inducing chromosome segregation errors by Mps1 inhibition in AML cell lines causes DNA damage, micronuclei formation, and upregulation of interferon stimulated genes. High levels of CIN appear to be immunostimulatory, suggesting an opportunity to combine mitotic checkpoint inhibitors with immunotherapy in treatment of AML.
Details
- Title: Subtitle
- Chromosomal instability upregulates interferon in acute myeloid leukemia
- Creators
- Ning Jin - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USARobert F. Lera - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USARachel E. Yan - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USAFen Guo - Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin State Lab Hyg, Madison, WI 53705 USAKim Oxendine - Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin State Lab Hyg, Madison, WI 53705 USAVanessa L. Horner - Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin State Lab Hyg, Madison, WI 53705 USAYang Hu - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USAJun Wan - Univ Wisconsin, Dept Oncol, McArdle Lab Canc Res, Madison, WI 53705 USARyan J. Mattison - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USABeth A. Weaver - Univ Wisconsin, Dept Oncol, McArdle Lab Canc Res, Madison, WI 53705 USAMark E. Burkard - Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI 53705 USA
- Resource Type
- Journal article
- Publication Details
- Genes chromosomes & cancer, Vol.59(11), pp.627-638
- DOI
- 10.1002/gcc.22880
- PMID
- 32557940
- PMCID
- PMC7597364
- NLM abbreviation
- Genes Chromosomes Cancer
- ISSN
- 1045-2257
- eISSN
- 1098-2264
- Publisher
- Wiley
- Number of pages
- 12
- Grant note
- HL007899 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 16PRE29650011 / American Heart Association CA014520; CA234904 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 11/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984700651902771
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