CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia

Biernacki, Melinda A.; Foster, Kimberly A.; Woodward, Kyle B.; Coon, Michael; Cummings, Carrie L.; Cunningham, Tanya; Dossa, Robson G.; Brault, Michelle; Stokke, Jamie; Olsen, Tayla M.; Gardner, Kelda M.; Estey, Elihu H.; Meshinchi, Soheil; Rongvaux, Anthony; Bleakley, Marie

doi:10.1172/jci137723

Cited by 59 publications

(48 citation statements)

References 91 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, antitumoral immunity, or the response to immunotherapies, can be highly variable from experiment to experiment ( 171 ). In the case of hematologic malignancies, new strains of recipient mice (i.e., MISTRG and MISTRG6) extend the range of transplantable diseases ( 72 , 133 – 136 ) and provide new opportunities to evaluate candidate immunotherapies, such as adoptive T cell therapies ( 174 , 175 ).…”

Section: Future Challenge #4: Interactions Between Immune Cells and Tmentioning

confidence: 99%

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

Since the late 1980s, mice have been repopulated with human hematopoietic cells to study the fundamental biology of human hematopoiesis and immunity, as well as a broad range of human diseases in vivo. Multiple mouse recipient strains have been developed and protocols optimized to efficiently generate these “humanized” mice. Here, we review three guiding principles that have been applied to the development of the currently available models: (1) establishing tolerance of the mouse host for the human graft; (2) opening hematopoietic niches so that they can be occupied by human cells; and (3) providing necessary support for human hematopoiesis. We then discuss four remaining challenges: (1) human hematopoietic lineages that poorly develop in mice; (2) limited antigen-specific adaptive immunity; (3) absent tolerance of the human immune system for its mouse host; and (4) sub-functional interactions between human immune effectors and target mouse tissues. While major advances are still needed, the current models can already be used to answer specific, clinically-relevant questions and hopefully inform the development of new, life-saving therapies.

show abstract

Section: Future Challenge #4: Interactions Between Immune Cells and Tmentioning

confidence: 99%

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…There have been some reports on the effect of MYH11 on cancer. Studies have con rmed that it is related to the pathogenesis or prognosis of lung cancer, acute myeloid leukemia, gastric cancer, colorectal cancer and breast cancer [24][25][26][27]. However, the relationship between MYH11 and Hypopharyngeal carcinoma has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Application Value of Whole Exome Sequencing in Screening and Identifying Pathogenic Genes of Hypopharyngeal Carcinoma

Yao

Ding

Liu

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Whole-exome sequencing has been used in many cancer research, but it is rarely used in Hypopharyngeal carcinoma. In our research, we performed whole-exome sequencing of DNA from 10 tumor tissue specimens from patients with hypopharyngeal cancer rather than targeted sequencing of specific genes.Methods: Whole-exome sequencing in 10 patients with hypopharyngeal carcinoma was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. Gene Ontology (GO) and pathway enrichment were used to analyze the function and effect of mutated genes. Protein protein interaction (PPI) was analyzed by string online software.Results: 8113 mutation sites in 5326 genes were identified after strict screening. MEGF8, ITPR1, DYSF, DNAH10, CUL7, MYH14, LRP1, ASTN1, TTN, ASH1L, MYH11, KMT2C were mutated in more than 6 patients. We identified 72 pathogenic or potentially pathogenic mutations in 53 genes according to the ACMG guidelines. GO annotation and KEGG enrichment analysis show the possible effect of these pathogenic genes on cancer. Conclusion: We identified novel mutations in patients with hypopharyngeal cancer, and provided a foundation for future research on the pathogenesis of hypopharyngeal carcinoma and targeted treatment of hypopharyngeal carcinoma.

show abstract

“…As a key cofactor, HDAC1 participates in the forming of AML1: CBFβ-SMMHC complex, which is essential for the transcriptional activity of related genes, involving in leukemic cell differentiation block and pro-proliferation ( 125 ). Additionally, pharmacologic inhibition of HDAC1 contributes to the suppression of leukemogenesis with CBFβ-SMMHC ( 126 , 127 ). And in vivo , it can decrease the mouse leukemic burden, showing an effective role of HDAC1 targeting the CBFβ-SMMHC protein ( 30 ).…”

Section: Hdacs In Aml With Cbfβ-myh11mentioning

confidence: 99%

Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins

Zhang

Gao

2021

Front. Oncol.

View full text Add to dashboard Cite

Accurate orchestration of gene expression is critical for the process of normal hematopoiesis, and dysregulation is closely associated with leukemogenesis. Epigenetic aberration is one of the major causes contributing to acute myeloid leukemia (AML), where chromosomal rearrangements are frequently found. Increasing evidences have shown the pivotal roles of histone deacetylases (HDACs) in chromatin remodeling, which are involved in stemness maintenance, cell fate determination, proliferation and differentiation, via mastering the transcriptional switch of key genes. In abnormal, these functions can be bloomed to elicit carcinogenesis. Presently, HDAC family members are appealing targets for drug exploration, many of which have been deployed to the AML treatment. As the majority of AML events are associated with chromosomal translocation resulting in oncogenic fusion proteins, it is valuable to comprehensively understand the mutual interactions between HDACs and oncogenic proteins. Therefore, we reviewed the process of leukemogenesis and roles of HDAC members acting in this progress, providing an insight for the target anchoring, investigation of hyperacetylated-agents, and how the current knowledge could be applied in AML treatment.

show abstract

CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia

Cited by 59 publications

References 91 publications

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

Building the Next Generation of Humanized Hemato-Lymphoid System Mice

Application Value of Whole Exome Sequencing in Screening and Identifying Pathogenic Genes of Hypopharyngeal Carcinoma

Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins

Contact Info

Product

Resources

About