Post-graduate theses
Current Record: 5182 of 6695
|
Identifier |
000376420 |
Title |
Characterization of bone marrow mesenchymal stem cells from patients with myeloid disorders using chromosomal analysis and molecular genetic techniques |
Alternative Title |
Χαρακτηρισμός των αρχέγονων μεσεγχυματικών κυττάρων του μυελού των οστών σε ασθενείς με μυελικές διαταραχές χρησιμοποιώντας χρωμοσωμική ανάλυση και τεχνικές μοριακής γενετικής |
Author
|
Batsali, Aristea
|
Author
|
Μπάτσαλη, Αριστέα
|
Thesis advisor
|
Παπαδάκη, Ελένη
|
Abstract |
In bone marrow (BM) there are at least two types of multipotent stem cells:
hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Although in
general these two cell types are distinct as regards their origin and differentiation
potential, there are some indirect evidence supporting that HSCs and MSCs may
have their origin from a common ancestor stem cell.
The aim of this study is to investigate whether the abnormal clone in acute
myeloid leukemia (AML) -, myelodysplastic syndromes (MDS) - or myeloproliferative
syndromes (MPD) – patients, derives from the aforementioned common ancestor
stem cell of HSCs and MSCs. To answer this question we assessed whether the
associated with myeloid malignancy mutations and chromosomal aberrations
detected in hematopoietic cells of patients, were also found in patient MSCs.
We studied 16 MDS patients, 12 AML and 7 MPD, and 10 healthy age- and
sex-matched individuals. DNA and RNA were isolated from the mononuclear myeloid
cell fraction and cultured marrow MSCs. The presence of mutations in FLT3 gene
was evaluated by genomic DNA PCR and the presence of mutations in the NPM1
gene in patients with MDS and AML was assessed by RT-PCR. The presence of
mutation V617F/G1849T in JAK2 gene was detected by real time RT-PCR in patients
with MPD. Moreover, MSCs and hematopoietic cells were subjected into cytogenetic
analysis.
In the total of MDS and AML patients, two AML patients were identified with
gene mutations in bone marrow mononuclear cells: one harbored mutations in FLT3
and NPM1 genes and the other harbored a mutation in NPM1 gene. Four MPD
patients were positive for the JAK2 mutation in bone marrow mononuclear cells. In
respect to MSCs, none of the 35 patients harbored any of these mutations.
Furthermore none of the healthy individuals harbored mutations in marrow
mononuclear cells or MSCs. In 6/28 of MDS or AML patients, chromosomal
abnormalities were identified in HSCs, and 1/28 in corresponding MSCs. Finally, two
of healthy subjects were identified with chromosomal abnormalities in MSCs, but the
corresponding HSCs were normal. In view of these data, this study gives further
confirm to the absence of clonal involvement of MSCs in hematological malignancies,
especially in AML, MDS and MPD.
|
Language |
Greek |
Subject |
Acute myeloid leukemia |
|
Chromosomal aberration |
|
FLT3 |
|
Genetic mutation |
|
JAK2 |
|
Mesenchymal stem cells |
|
Myelodysplastic syndrome |
|
Myeloproliferative disease |
|
NPM1 |
|
Μεσεγχυματικά κύτταρα |
|
Μυελοδυσπλαστικό σύνδρομο |
|
Μυελουπερπλαστικό σύνδρομο |
|
Οξεία μυελογενής λευχαιμία |
Issue date |
2011-12-15 |
Collection
|
School/Department--School of Medicine--Department of Medicine--Post-graduate theses
|
|
Type of Work--Post-graduate theses
|
Permanent Link |
https://elocus.lib.uoc.gr//dlib/f/c/a/metadata-dlib-1352973924-695926-20186.tkl
|
Views |
243 |