Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia
Аутори
Karan-Đurašević, TeodoraKaćanski, Nataša
Kostić, Tatjana
Marjanović, Irena
Tošić, Nataša
Perić, Jelena
Kolarović, Jovanka
Janić, Dragana
Pavlović, Sonja
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to
birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of
childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements.
Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient
and used in semi-nested PCR for the detection of preleukemic clones at birth.
Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In
two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at
birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie
card-positive findings were... significantly more frequent in children ≤5 years of age than in older children
(p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of
bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes
at diagnosis.
Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt
leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events.
Кључне речи:
childhood acute lymphoblastic leukemia / prenatal origin / Guthrie cards / immunoglobulin heavy chain rearrangementsИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 59-59Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Karan-Đurašević, Teodora AU - Kaćanski, Nataša AU - Kostić, Tatjana AU - Marjanović, Irena AU - Tošić, Nataša AU - Perić, Jelena AU - Kolarović, Jovanka AU - Janić, Dragana AU - Pavlović, Sonja PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2113 AB - Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements. Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient and used in semi-nested PCR for the detection of preleukemic clones at birth. Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis. Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events. PB - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia EP - 59 SP - 59 UR - https://hdl.handle.net/21.15107/rcub_imagine_2113 ER -
@conference{ author = "Karan-Đurašević, Teodora and Kaćanski, Nataša and Kostić, Tatjana and Marjanović, Irena and Tošić, Nataša and Perić, Jelena and Kolarović, Jovanka and Janić, Dragana and Pavlović, Sonja", year = "2023", abstract = "Introduction: Childhood B-cell precursor acute lymphoblastic leukemic (BCP-ALL) can be traced back to birth using leukemic clone-specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease. The aim of this study was to analyze neonatal blood spots (Guthrie cards) of childhood BCP-ALL patients for the presence of clonotypic IGH rearrangements. Methods: The study enrolled 24 patients aged 1 to 9.6 years. Based on the sequences of IGH rearrangements identified in diagnostic lymphoblasts, 2 patient-specific primers were designed for each patient and used in semi-nested PCR for the detection of preleukemic clones at birth. Results: Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients. In two cases that had double IGH rearrangements at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card-positive findings were significantly more frequent in children ≤5 years of age than in older children (p=0.011). Regarding patients’characteristics at birth and at diagnosis, Guthrie card-positivity was not associated with sex, birth weight and mother’s age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis. Conclusion: Our study confirms that a large proportion of childhood BCP-ALL originates in utero, regardless of the molecularsubtype defined by chromosomal aberrations. The latency period to the overt leukemia depends on the presence of preleukemic clone at birth, as well as on the postnatal transforming genetic events.", publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia", pages = "59-59", url = "https://hdl.handle.net/21.15107/rcub_imagine_2113" }
Karan-Đurašević, T., Kaćanski, N., Kostić, T., Marjanović, I., Tošić, N., Perić, J., Kolarović, J., Janić, D.,& Pavlović, S.. (2023). Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 59-59. https://hdl.handle.net/21.15107/rcub_imagine_2113
Karan-Đurašević T, Kaćanski N, Kostić T, Marjanović I, Tošić N, Perić J, Kolarović J, Janić D, Pavlović S. Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:59-59. https://hdl.handle.net/21.15107/rcub_imagine_2113 .
Karan-Đurašević, Teodora, Kaćanski, Nataša, Kostić, Tatjana, Marjanović, Irena, Tošić, Nataša, Perić, Jelena, Kolarović, Jovanka, Janić, Dragana, Pavlović, Sonja, "Detection of preleukemic clones in neonatal blood spots of children with B-cell precursor acute lymphoblastic leukemia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):59-59, https://hdl.handle.net/21.15107/rcub_imagine_2113 .