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Inducing MLL-AF4 in different hematopoietic stem and progenitor cells to study the initiation of childhood B cell leukemia

Calderon Moreno, Ariana (2020) MOBM02 20201
Degree Projects in Molecular Biology
Popular Abstract
Investigating the initiation of childhood leukemia

Leukemia is a cancer of the early blood-forming cells, causing a rise in the number of white blood cells in your body. These extra white blood cells can’t fight an infection the way normal white blood cells do. This also causes a reduction on red blood cells, that supply oxygen, and also a reduction on platelets that clot the blood. Due to this some of the most common symptoms of leukemia are anemia; infection and bleeding. Acute lymphoblastic leukemia (ALL) is the most common type of leukemia among pediatric patients but so far little is known about the initiation of ALL.

It is known that the change in the genetic code (mutation) causing the cells to become leukemic happens during... (More)
Investigating the initiation of childhood leukemia

Leukemia is a cancer of the early blood-forming cells, causing a rise in the number of white blood cells in your body. These extra white blood cells can’t fight an infection the way normal white blood cells do. This also causes a reduction on red blood cells, that supply oxygen, and also a reduction on platelets that clot the blood. Due to this some of the most common symptoms of leukemia are anemia; infection and bleeding. Acute lymphoblastic leukemia (ALL) is the most common type of leukemia among pediatric patients but so far little is known about the initiation of ALL.

It is known that the change in the genetic code (mutation) causing the cells to become leukemic happens during fetal life. One of the most common mutations in childhood ALL is MLL-AF4, causing a very aggressive disease with poor prognosis. The focus of this project was to understand how MLL-AF4 is affecting different cell types and try to identify a possible target cell for the initiation of childhood leukemia.

To achieve this, we used a mouse model, where we could target different cell populations with MLL-AF4. We studied three cell populations, first, the hematopoietic stem cells (HSCs) with the ability to give rise to all of the different mature blood cell types. Second, early lymphoid/myeloid progenitors (LMPPs), that are cells giving rise to the white blood cells and finally the B cells. B cells are able to fight an infection and are the main affected population in ALL.

Our data indicates no difference on the B cells with and without the mutation, suggesting that this is not the cell population where the leukemia starts. We saw a reduction on lymphoid cells and an increase on myeloid cells when we target the HSCs, suggesting a possible target cell at the level of an HSCs or a lymphoid-myeloid primed progenitor. The results presented here help us in some way to understand how this disease starts. Such knowledge may in the future help to develop new therapeutic targets with less secondary effects.


Master’s Degree Project in Molecular Biology 30 credits 2020
Department of Biology, Lund University
Supervisor: Charlotta Boiers
Division of molecular hematology, BMC B12 (Less)
Please use this url to cite or link to this publication:
author
Calderon Moreno, Ariana
supervisor
organization
course
MOBM02 20201
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9028746
date added to LUP
2020-09-09 14:23:37
date last changed
2020-09-09 14:23:37
@misc{9028746,
  author       = {Calderon Moreno, Ariana},
  language     = {eng},
  note         = {Student Paper},
  title        = {Inducing MLL-AF4 in different hematopoietic stem and progenitor cells to study the initiation of childhood B cell leukemia},
  year         = {2020},
}