AMPLIFICATION OF c-MYC AND MLL GENES
AS A MARKER OF CLONAL CELL PROGRESSION
IN PATIENTS WITH MYELOID MALIGNANCY
AND TRISOMY OF CHROMOSOMES 8 OR 11
Angelova S1,*, Jordanova M2, Spassov B1, Shivarov V1, Simeonova M3,
Christov I4, Angelova P3, Alexandrova K5, Stoimenov A1, Nikolova V1,
Dimova I6, Ganeva P1, Tzvetkov N4, Hadjiev E5, Toshkov S1
*Corresponding Author: Svetlana Angelova, Biologist, Laboratory of Cytogenetics and Molecular Biology,
National Specialized Hospital for Active Therapy of Hematological Diseases, 6, «Plovdivsko pole», Sofia, 1756,
Bulgaria; Tel.: +35929701133; Fax : +35929701107; E-mail: sv_angelru@abv.bg
page: 17
|
|
PATIENTS AND METHODS
Patient Group. A total of 26 patients aged 16 to
82 years (median about 62 years) were included in this
study. The distribution at diagnosis was: 16 patients
with overt AML, seven with secondary AML after
MDS (sAML) and three with different types of MDS.
Eighteen patients had +8; in half of them the tri- or
tetrasomy 8 was a sole cytogenetic abnormality. There
were additional karyotipical aberrations in the other
nine cases. It was the only anomaly in three of the six
cases with +11; the karyotypes in the other three cases
were more complicated. Also included were two additional
cases with complex karyotypes suspected for
amp MLL. All patients with AML below or equal to 65
(≤65) years of age were treated with induction therapy
consisting of antharacycline (Idarubicine, Farmorubicine
or Mitoxantrone) and cytarabine according to the
standard protocols. Patients above 65 (>65) years of
age received chemotherapy with Cytosar only. Patients
with MDS before transformation to AML received supportive
therapy and after transformation were treated
with standard chemotherapy. The study was approved
by the local Ethics Committee of the National Hospital
for Hematological Diseases. All participants had given
written informed consent.
Cytogenetic Analysis. Routine cytogenetic analysis
was performed on metaphase chromosomes from
bone marrow samples using a direct method and after
short-term 24- or 48 hour-culturing [18]. A minimum
of 15 bone marrow metaphase cells were analyzed in
each patient using GTG differentially-stained chromosomes
at a discriminatory level of 300-400 bands per
haploid count. Karyotypic findings were interpreted
and described according to the International System for
Human Cytogenetic Nomenclature (ISCN, 2009) [19].
Fluorescent In Situ Hybridization (FISH). Fluorescent
in situ hybridization was performed according
to the standard manufacturer’s protocol (Vysis®;
Abbot Molecular Inc., Abbott Park, IL, USA) on interphase
nuclei in suspension after a routine cytogenetic
procedure and stored at –20°Ñ. Locus-specific dual
color MLL break apart rearrangement probe and c-
MYC break apart rearrangement probe (Vysis®; Abbot
Molecular Inc.) were used, and no less than 200 interphase
nuclei per probe were analyzed. In these probes,the 5’ portion of the MLL gene (or c-MYC) was labeled
in green, and the 3’ portion in red. Thus, the presence
of two normal gene signals in the cell was visualized
as dual composite signals (red + green). The gene deletion
was detected as a single composite signal, and +8
(or +11) as three composite signals. The presence of
more than three composite signals was considered as a
MLL (or c-MYC) gene amp. We recognized amplification
level as a significant if amp were observed in more
than 10% of interphase nuclei, under the 10%, as a low
level amp.
|
|
|
|
 |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
|
