Publication

Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity

Mattes, K., 2019, [Groningen]: Rijksuniversiteit Groningen. 155 p.

Research output: ThesisThesis fully internal (DIV)Academic

APA

Mattes, K. (2019). Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity. [Groningen]: Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.98637951

Author

Mattes, Katharina. / Biology of acute myeloid leukemia stem cells : the role of CITED2 and mitochondrial activity. [Groningen] : Rijksuniversiteit Groningen, 2019. 155 p.

Harvard

Mattes, K 2019, 'Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity', Doctor of Philosophy, University of Groningen, [Groningen]. https://doi.org/10.33612/diss.98637951

Standard

Biology of acute myeloid leukemia stem cells : the role of CITED2 and mitochondrial activity. / Mattes, Katharina.

[Groningen] : Rijksuniversiteit Groningen, 2019. 155 p.

Research output: ThesisThesis fully internal (DIV)Academic

Vancouver

Mattes K. Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity. [Groningen]: Rijksuniversiteit Groningen, 2019. 155 p. https://doi.org/10.33612/diss.98637951


BibTeX

@phdthesis{5b7f54456ab34f58841e893124a8d536,
title = "Biology of acute myeloid leukemia stem cells: the role of CITED2 and mitochondrial activity",
abstract = "Acute myeloid leukemia (AML) is a form of blood cancer that affects the myeloid lineage of blood cells and is characterized by the accumulation of immature myeloid blasts in the bone marrow. The prognosis for patients with AML is currently still rather poor, mainly due to disease relapse. Whereas current standard chemotherapy strategies lead to an initial reduction of leukemic blasts in the majority of patients, a small cell population persists and is apparently not efficiently targeted, leading to recurrence of the disease. Evidence exists that relapse is initiated by leukemia stem cells (LSCs), and analysis of the molecular mechanisms that drive their stemness- and drug-resistant- properties is necessary to improve AML therapy. The maintenance of hematopoietic stem cells and their differentiation into mature blood cells is regulated by a complex network of different proteins, including the in AML frequently deregulated proteins CITED2 and PU.1. The first part of this thesis focuses on analyzing the role of CITED2 and PU.1 in AML cell survival and stem cell maintenance, as well as in processes preceding malignant transformation. Reduction of CITED2 levels in AML cells is highlighted as a potential therapy strategy.The second part of this thesis aims to analyze metabolic properties of LSCs and demonstrates that AML cells with low mitochondrial activity have a high expression of genes linked to stem cell maintenance and chemotherapy resistance, and therefore likely coincide with the LSCs. It is demonstrated that these cells can be efficiently targeted by inhibition of the mitochondrial regulator BCL2.",
author = "Katharina Mattes",
year = "2019",
doi = "10.33612/diss.98637951",
language = "English",
isbn = "978-94-028-1723-2",
publisher = "Rijksuniversiteit Groningen",
school = "University of Groningen",

}

RIS

TY - THES

T1 - Biology of acute myeloid leukemia stem cells

T2 - the role of CITED2 and mitochondrial activity

AU - Mattes, Katharina

PY - 2019

Y1 - 2019

N2 - Acute myeloid leukemia (AML) is a form of blood cancer that affects the myeloid lineage of blood cells and is characterized by the accumulation of immature myeloid blasts in the bone marrow. The prognosis for patients with AML is currently still rather poor, mainly due to disease relapse. Whereas current standard chemotherapy strategies lead to an initial reduction of leukemic blasts in the majority of patients, a small cell population persists and is apparently not efficiently targeted, leading to recurrence of the disease. Evidence exists that relapse is initiated by leukemia stem cells (LSCs), and analysis of the molecular mechanisms that drive their stemness- and drug-resistant- properties is necessary to improve AML therapy. The maintenance of hematopoietic stem cells and their differentiation into mature blood cells is regulated by a complex network of different proteins, including the in AML frequently deregulated proteins CITED2 and PU.1. The first part of this thesis focuses on analyzing the role of CITED2 and PU.1 in AML cell survival and stem cell maintenance, as well as in processes preceding malignant transformation. Reduction of CITED2 levels in AML cells is highlighted as a potential therapy strategy.The second part of this thesis aims to analyze metabolic properties of LSCs and demonstrates that AML cells with low mitochondrial activity have a high expression of genes linked to stem cell maintenance and chemotherapy resistance, and therefore likely coincide with the LSCs. It is demonstrated that these cells can be efficiently targeted by inhibition of the mitochondrial regulator BCL2.

AB - Acute myeloid leukemia (AML) is a form of blood cancer that affects the myeloid lineage of blood cells and is characterized by the accumulation of immature myeloid blasts in the bone marrow. The prognosis for patients with AML is currently still rather poor, mainly due to disease relapse. Whereas current standard chemotherapy strategies lead to an initial reduction of leukemic blasts in the majority of patients, a small cell population persists and is apparently not efficiently targeted, leading to recurrence of the disease. Evidence exists that relapse is initiated by leukemia stem cells (LSCs), and analysis of the molecular mechanisms that drive their stemness- and drug-resistant- properties is necessary to improve AML therapy. The maintenance of hematopoietic stem cells and their differentiation into mature blood cells is regulated by a complex network of different proteins, including the in AML frequently deregulated proteins CITED2 and PU.1. The first part of this thesis focuses on analyzing the role of CITED2 and PU.1 in AML cell survival and stem cell maintenance, as well as in processes preceding malignant transformation. Reduction of CITED2 levels in AML cells is highlighted as a potential therapy strategy.The second part of this thesis aims to analyze metabolic properties of LSCs and demonstrates that AML cells with low mitochondrial activity have a high expression of genes linked to stem cell maintenance and chemotherapy resistance, and therefore likely coincide with the LSCs. It is demonstrated that these cells can be efficiently targeted by inhibition of the mitochondrial regulator BCL2.

U2 - 10.33612/diss.98637951

DO - 10.33612/diss.98637951

M3 - Thesis fully internal (DIV)

SN - 978-94-028-1723-2

PB - Rijksuniversiteit Groningen

CY - [Groningen]

ER -

ID: 98637951