Premium
Chromosomal instability upregulates interferon in acute myeloid leukemia
Author(s) -
Jin Ning,
Lera Robert F.,
Yan Rachel E.,
Guo Fen,
Oxendine Kim,
Horner Vanessa L.,
Hu Yang,
Wan Jun,
Mattison Ryan J.,
Weaver Beth A.,
Burkard Mark E.
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22880
Subject(s) - chromosome instability , myeloid leukemia , cancer research , biology , bone marrow , cancer , myeloid , mitosis , aneuploidy , philadelphia chromosome , chromosome , immunology , oncology , medicine , chromosomal translocation , gene , genetics
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.