Τομέας Παθολογίας
Library of the School of Health Sciences

2013-06-17

2013

Γκίρκας Κωνσταντίνος

Καθηγητής Σ. Ράπτης, Καθηγητής Θ. Οικονομόπουλος, Καθηγητής Ι. Δερβενούλας

Διερεύνηση μεταλλάξεων του μιτοχονδριακού DNA σε πρωτοπαθή μυελοδυσπλαστικά σύνδρομα

Greek

Mitochondria play an important role in both apoptosis and haem synthesis.
Given the appreciation of their significant contribution to maintain cellular
homeostasis it is not surprising that mitochondrial mutations are associated
with a variety of both congenital diseases (Pearson’s syndrome) as well as
acquired ones such as various cancers.
Due to their significant contribution to the regulation of haem synthesis and
apoptosis, we were interested in investigating the role of mitochondrial DNA
mutations in Myelodysplastic syndromes in which iron laden mitochondria are
associated with variable cytopenias and apoptosis of hematopoietic cells and
correlate the findings with clinical characteristics as well as to the level of
apoptosis.
Our analysis included 55 cases of de novo MDS (38 male, 17 female) with a
median age 71.5 (43-87). In 29/55 cases apoptosis was calculated by flow
cytometry on freshly isolated total bone marrow mononuclear cells as well as on
CD34+ cells. Early apoptotic cells were classified as Annexin V + cells and
late apoptotic as Annexin V+/PI + cells.
Of the 55 cases, 47 were analyzed for mitochondrial cytochrome c-oxidase I and
II gene mutations using PCR amplification and direct sequencing analysis.
Bone marrow cells from 13 patients with lymphoma without bone marrow
involvement were used as controls.
RESULTS
• No statistically significant difference was found between early and
late apoptosis of total cells and CD34+ cells in patients with MDS and normal
controls.
• No statistically significant association was detected between all
these parameters and FAB, WHO and IPSS classifications.
• However, a significant higher median value of CD34+ late apoptotic
cells was found in cases with  5% bone marrow blast percentage.
• Moreover, the median percentage value of late apoptosis was
significantly higher in total bone marrow mononuclear cells compared to CD34+
cells.
• The analysis of Cytochrome C I and II gene mutations detected 3/47
cases with mutations: One case with RAEB-II and Intermediate-II IPSS was
characterized by a silent T to C change at nt position 7374 of cytochrome
C-oxidase I gene, a second case with RARS and intermediate-I IPSS had a C to T
change at nt 7868 of cytochrome C-oxidase II gene resulting in Leu to Phe
substitution and a case with RAEB-I and Intermediate-I IPSS had a silent C to T
change at nt 7875 of the same gene.
CONCLUSIONS
 In our series, cases with blast percentage  5% were characterized by
significantly higher numbers of late apoptotic CD34+ cells.
 Late apoptosis is significantly higher in total mature bone marrow
cells compared to primitive CD34+ cells.
 Cytochrome C oxidase I and II gene mutations were not a frequent
phenomenon, detected in 6.4 % of cases.
 It is interesting to note that 1/3 cases with RARS was characterized
by a cytochrome C-oxidase II gene mutation resulting in aminoacid substitution,
stressing the importance of these mutations in this MDS subtype.
 The biological significance of mitochondrial gene mutations and their
relation to apoptosis remains to be determined by screening a larger number of
MDS cases.

Myelodysplastic syndromes, Apoptosis, Cytochrome, Mitochondria, Cytochrome oxidase

Yes

5

Yes

221

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https://pergamos.lib.uoa.gr/uoa/dl/object/1305999