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°Ń. 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

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006