fstaya.blogg.se - Altered fate

Epigenetic memory is controlled by chromatin regulators that enable and enforce selective gene expression. A phenomenon where daughter cells inherit information from the mother cell following cell division.The development and maturation of a cell over time.In the context of cancer, differentiation therapy is intended to convert cells from a self-renewing to a non-self-renewing phenotype. A therapeutic strategy that induces the conversion of cellular states.A phenomenon whereby cells are not able to follow their normal maturation to become a terminally differentiated and fully functional effector cell.Differentiation is underpinned by alterations in the chromatin and transcriptional states of the cell. The process by which the features, function, or potential of a cell is altered, e.g., conversion of a multi-potent stem cell to a lineage-committed progenitor.Conversion of a mature or terminally differentiated cell to a stem-like cell.In the context of leukemia, CSCs are referred to as leukemic stem cells (LSCs). CSCs share many features with normal stem cells.

A type of malignant cell is capable of limitless self-renewal and is thought to be responsible for tumor maintenance and propagation.Cells at the top levels (e.g., stem or multi-potent progenitor cells) can give rise to cells at lower levels (e.g., restricted progenitors or effector cells), but not vice versa.

In some tissues, cells are hierarchically organized.

The capacity of a cell to reprogram its transcriptional and epigenetic state and adopt a new phenotype.

Herein, we will review recent developments that are providing unprecedented insights into non-genetic heterogeneity both at steady state and in response to treatment, and propose a new conceptual framework for therapies that aim to alter cell fate decisions in cancer. Notionally however, the simplistic view that such agents “unblock” differentiation is at odds with the cancer stem cell (CSC) hypothesis that posits that tumors are hierarchically organized and that CSCs, which underpin cancer growth, retain the capacity to progress to a developmentally more mature state. Classically, the defining properties of AML cells were said to be aberrant self-renewal and a block of differentiation, and the term “differentiation therapy” was coined to describe drugs that promote the maturation of leukemic blasts. Among the malignancies where processes that govern cell fate decisions have been studied most extensively is acute myeloid leukemia (AML), a disease characterized by the presence of large numbers of “blasts” that resemble myeloid progenitors. Altered capacity for self-renewal and differentiation is a hallmark of cancer, and many tumors are composed of cells with a developmentally immature phenotype.