Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review

Introduction. The isochromosome of the long arm of derivative chromosome 17, that originates from the translocation t(15;17) [ider(17)(q10)t(15;17), or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration associated with a poor prognosis. Case report. We report the clini...

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Main Authors: Đorđević Vesna, Denčić-Fekete Marija, Jovanović Jelica, Virijević Marijana, Kraguljac-Kurtović Nada, Jaković Ljubomir, Bogdanović Andrija
Format: Article
Language:English
Published: Ministry of Defence of the Republic of Serbia, University of Defence, Belgrade 2019-01-01
Series:Vojnosanitetski Pregled
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Online Access:http://www.doiserbia.nb.rs/img/doi/0042-8450/2019/0042-84501700174D.pdf
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author Đorđević Vesna
Denčić-Fekete Marija
Jovanović Jelica
Virijević Marijana
Kraguljac-Kurtović Nada
Jaković Ljubomir
Bogdanović Andrija
author_facet Đorđević Vesna
Denčić-Fekete Marija
Jovanović Jelica
Virijević Marijana
Kraguljac-Kurtović Nada
Jaković Ljubomir
Bogdanović Andrija
author_sort Đorđević Vesna
collection DOAJ
description Introduction. The isochromosome of the long arm of derivative chromosome 17, that originates from the translocation t(15;17) [ider(17)(q10)t(15;17), or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration associated with a poor prognosis. Case report. We report the clinical and laboratory data associated with ider(17q) for two APL patients. Cytogenetic analysis of bone marrow cells in both cases showed a mosaic karyotype with the ider(17q); reverse transcription polymerase chain reaction (RT-PCR) was positive for the long (L) isoform of the retionic acid receptor alpha (PML-RARA) fusion transcript in each patient. Fluorescence in situ hybridization (FISH) analysis with the DNA probes for the PML gene on 15q24.1, and the RARA gene on 17q21.2, confirmed the extra copy of the RARA-PML fusion gene or ider(17q). Additionally, the FISH analysis with a DNA probe for the p53 gene on 17p13.1 confirmed loss of one copy of the universal tumor suppressor p53 in both patients. Conclusion. Both reported APL patients with ider(17q) had predominance of the clone with ider(17q) compared to those with t(15;17) and/or the normal karyotype, indicating that duplication of der(17) may provide a growth advantage allowing the relevant clone to become dominant. Moreover, as an important oncogenic event and poor prognostic factor in leukemia, loss of one gene copy of the tumor suppressor p53, may also contribute to this growth advantage. Although the clinical and prognostic significance for the patients with an ider(17q) remains unclear, cytogenetic and molecular-genetic analysis should be combined to reveal more details about this complex and rare chromosomal abnormality. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 41004]
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spelling doaj-art-efffddfcb27040ab9ff44850e3b5c9aa2025-08-20T02:22:03ZengMinistry of Defence of the Republic of Serbia, University of Defence, BelgradeVojnosanitetski Pregled0042-84502406-07202019-01-0176996096710.2298/VSP170824174D0042-84501700174DIsochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature reviewĐorđević Vesna0Denčić-Fekete Marija1Jovanović Jelica2Virijević Marijana3Kraguljac-Kurtović Nada4Jaković Ljubomir5Bogdanović Andrija6Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia + University of Belgrade, Faculty of Medicine, Belgrade, SerbiaClinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia + University of Belgrade, Faculty of Medicine, Belgrade, SerbiaClinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia + University of Belgrade, Faculty of Medicine, Belgrade, SerbiaIntroduction. The isochromosome of the long arm of derivative chromosome 17, that originates from the translocation t(15;17) [ider(17)(q10)t(15;17), or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration associated with a poor prognosis. Case report. We report the clinical and laboratory data associated with ider(17q) for two APL patients. Cytogenetic analysis of bone marrow cells in both cases showed a mosaic karyotype with the ider(17q); reverse transcription polymerase chain reaction (RT-PCR) was positive for the long (L) isoform of the retionic acid receptor alpha (PML-RARA) fusion transcript in each patient. Fluorescence in situ hybridization (FISH) analysis with the DNA probes for the PML gene on 15q24.1, and the RARA gene on 17q21.2, confirmed the extra copy of the RARA-PML fusion gene or ider(17q). Additionally, the FISH analysis with a DNA probe for the p53 gene on 17p13.1 confirmed loss of one copy of the universal tumor suppressor p53 in both patients. Conclusion. Both reported APL patients with ider(17q) had predominance of the clone with ider(17q) compared to those with t(15;17) and/or the normal karyotype, indicating that duplication of der(17) may provide a growth advantage allowing the relevant clone to become dominant. Moreover, as an important oncogenic event and poor prognostic factor in leukemia, loss of one gene copy of the tumor suppressor p53, may also contribute to this growth advantage. Although the clinical and prognostic significance for the patients with an ider(17q) remains unclear, cytogenetic and molecular-genetic analysis should be combined to reveal more details about this complex and rare chromosomal abnormality. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 41004]http://www.doiserbia.nb.rs/img/doi/0042-8450/2019/0042-84501700174D.pdfleukemia, myeloidchromosome abberationsin situ hybridization, fluorescencetranslocation, geneticgenes, p53mortalityretinoic acid receptor alpha
spellingShingle Đorđević Vesna
Denčić-Fekete Marija
Jovanović Jelica
Virijević Marijana
Kraguljac-Kurtović Nada
Jaković Ljubomir
Bogdanović Andrija
Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
Vojnosanitetski Pregled
leukemia, myeloid
chromosome abberations
in situ hybridization, fluorescence
translocation, genetic
genes, p53
mortality
retinoic acid receptor alpha
title Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
title_full Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
title_fullStr Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
title_full_unstemmed Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
title_short Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review
title_sort isochromosome der 17 q10 t 15 17 in acute promyelocytic leukemia resulting in an additional copy of the rara pml and loss of one p53 gene report of two cases and literature review
topic leukemia, myeloid
chromosome abberations
in situ hybridization, fluorescence
translocation, genetic
genes, p53
mortality
retinoic acid receptor alpha
url http://www.doiserbia.nb.rs/img/doi/0042-8450/2019/0042-84501700174D.pdf
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