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An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1.

07:00 EST 14th January 2020 | BioPortfolio

Summary of "An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1."

Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1);RUNX1-RUNX1T1, one of the core-binding factor leukemias, is one of the most common subtypes of AML with recurrent genetic abnormalities and is associated with a favorable outcome. The translocation leads to the formation of a pathological RUNX1-RUNX1T1 fusion that leads to the disruption of the normal function of the core-binding factor, namely, its role in hematopoietic differentiation and maturation. The consequences of this alteration include the recruitment of repressors of transcription, thus blocking the expression of genes involved in hematopoiesis, and impaired apoptosis. A number of concurrent and cooperating mutations clearly play a role in modulating the proliferative potential of cells, including mutations in KIT, FLT3, and possibly JAK2. RUNX1-RUNX1T1 also appears to interact with microRNAs during leukemogenesis. Epigenetic factors also play a role, especially with the recruitment of histone deacetylases. A better understanding of the concurrent mutations, activated pathways, and epigenetic modulation of the cellular processes paves the way for exploring a number of approaches to achieve cure. Potential approaches include the development of small molecules targeting the RUNX1-RUNX1T1 protein, the use of tyrosine kinase inhibitors such as dasatinib and FLT3 inhibitors to target mutations that lead to a proliferative advantage of the leukemic cells, and experimentation with epigenetic therapies. In this review, we unravel some of the recently described molecular pathways and explore potential therapeutic strategies.

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This article was published in the following journal.

Name: Blood advances
ISSN: 2473-9537
Pages: 229-238

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A transcriptional co-repressor that contains a MYND-type zinc finger (MYND DOMAIN) at its C-terminal and functions as a homo-oligomer. It associates with DNA-binding transcription factors, other repressor proteins, and HISTONE ACETYLTRANSFERASES to repress expression of genes involved in cell growth and differentiation such as MATRIX METALLOPROTEINASE 7 and TCF12. A CHROMOSOMAL TRANSLOCATION involving the RUNX1T1 and CORE BINDING FACTOR ALPHA 2 SUBUNIT (RUNX1) genes frequently occurs in cells of leukemia patients; the resulting fusion protein (AML1-ETO or RUNX1-RUNX1T1) plays a critical role in leukemogenesis.

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The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...


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