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Polycomb factor Phf19 controls cell growth and differentiation towards erythroid pathway in chronic myeloid leukemia cells

ABSTRACT: Polycomb group (PcG) of proteins are a group of highly conserved epigenetic regulators involved in many biological functions, such as embryonic development, cell proliferation and adult stem cell determination. PHD finger protein 19 (PHF19) is an associated factor of Polycomb Repressor Complex 2 (PRC2) up-regulated in different human cancers. In particular, myeloid leukemia cell lines show increased levels of PHF19, yet little is known about its function. Here, we have characterized the role of PHF19 in cell lines of a type of myeloid leukemia named chronic myeloid leukemia (CML). Thus, we have demonstrated that PHF19 depletion decreases cell proliferation and promotes differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through its epigenetic regulation of the cell cycle regulator p21. Furthermore, we have observed that MTF2, a PHF19 homolog, compensates at chromatin level for PHF19 depletion, instructing specific erythroid differentiation. Taken together, our results show that PHF19 is a key transcriptional regulator for cell fate determination and could be a potential target for myeloid leukemia treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164804 | GEO | 2021/04/12

REPOSITORIES: GEO

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Project description:Moore2004 - Chronic Myeloid Leukemic cells and T-lymphocytes interaction A mathematical model for the interaction of between cancer cells and immune system, involving CML cancer cells, naive and effector T-lymphocytes. This model is described in the article: A mathematical model for chronic myelogenous leukemia (CML) and T cell interaction. Moore H, Li NK. J. Theor. Biol. 2004 Apr; 227(4): 513-523 Abstract: In this paper, we propose and analyse a mathematical model for chronic myelogenous leukemia (CML), a cancer of the blood. We model the interaction between naive T cells, effector T cells, and CML cancer cells in the body, using a system of ordinary differential equations which gives rates of change of the three cell populations. One of the difficulties in modeling CML is the scarcity of experimental data which can be used to estimate parameters values. To compensate for the resulting uncertainties, we use Latin hypercube sampling (LHS) on large ranges of possible parameter values in our analysis. A major goal of this work is the determination of parameters which play a critical role in remission or clearance of the cancer in the model. Our analysis examines 12 parameters, and identifies two of these, the growth and death rates of CML, as critical to the outcome of the system. Our results indicate that the most promising research avenues for treatments of CML should be those that affect these two significant parameters (CML growth and death rates), while altering the other parameters should have little effect on the outcome. This model is hosted on BioModels Database and identified by: BIOMD0000000662. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Polycomb factor Phf19 controls cell growth and differentiation towards erythroid pathway in chronic myeloid leukemia cells

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