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Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy
We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. T...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999738/ https://www.ncbi.nlm.nih.gov/pubmed/35409391 http://dx.doi.org/10.3390/ijms23074019 |
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author | Semchenkova, Alexandra Mikhailova, Ekaterina Komkov, Alexander Gaskova, Marina Abasov, Ruslan Matveev, Evgenii Kazanov, Marat Mamedov, Ilgar Shmitko, Anna Belova, Vera Miroshnichenkova, Anna Illarionova, Olga Olshanskaya, Yulia Tsaur, Grigory Verzhbitskaya, Tatiana Ponomareva, Natalia Bronin, Gleb Kondratchik, Konstantin Fechina, Larisa Diakonova, Yulia Vavilova, Liudmila Myakova, Natalia Novichkova, Galina Maschan, Alexey Maschan, Michael Zerkalenkova, Elena Popov, Alexander |
author_facet | Semchenkova, Alexandra Mikhailova, Ekaterina Komkov, Alexander Gaskova, Marina Abasov, Ruslan Matveev, Evgenii Kazanov, Marat Mamedov, Ilgar Shmitko, Anna Belova, Vera Miroshnichenkova, Anna Illarionova, Olga Olshanskaya, Yulia Tsaur, Grigory Verzhbitskaya, Tatiana Ponomareva, Natalia Bronin, Gleb Kondratchik, Konstantin Fechina, Larisa Diakonova, Yulia Vavilova, Liudmila Myakova, Natalia Novichkova, Galina Maschan, Alexey Maschan, Michael Zerkalenkova, Elena Popov, Alexander |
author_sort | Semchenkova, Alexandra |
collection | PubMed |
description | We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. Therefore, lineage conversion was found in 17.4% of all resistance cases (4/27) and 3.2% of relapses (2/63). Half of patients switched completely from BCP-ALL to CD19-negative acute myeloid leukemia, others retained CD19-positive B-blasts and acquired an additional CD19-negative blast population: myeloid or unclassifiable. Five patients had KMT2A gene rearrangements; one had TCF3::ZNF384 translocation. The presented cases showed consistency of gene rearrangements and fusion transcripts across initially diagnosed leukemia and lineage switch. In two of six patients, the clonal architecture assessed by IG/TR gene rearrangements was stable, while in others, loss of clones or gain of new clones was noted. KMT2A-r patients demonstrated very few additional mutations, while in the TCF3::ZNF384 case, lineage switch was accompanied by a large set of additional mutations. The immunophenotype of an existing leukemia sometimes changes via different mechanisms and with different additional molecular changes. Careful investigation of all BM compartments together with all molecular –minimal residual disease studies can lead to reliable identification of lineage switch. |
format | Online Article Text |
id | pubmed-8999738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89997382022-04-12 Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy Semchenkova, Alexandra Mikhailova, Ekaterina Komkov, Alexander Gaskova, Marina Abasov, Ruslan Matveev, Evgenii Kazanov, Marat Mamedov, Ilgar Shmitko, Anna Belova, Vera Miroshnichenkova, Anna Illarionova, Olga Olshanskaya, Yulia Tsaur, Grigory Verzhbitskaya, Tatiana Ponomareva, Natalia Bronin, Gleb Kondratchik, Konstantin Fechina, Larisa Diakonova, Yulia Vavilova, Liudmila Myakova, Natalia Novichkova, Galina Maschan, Alexey Maschan, Michael Zerkalenkova, Elena Popov, Alexander Int J Mol Sci Article We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. Therefore, lineage conversion was found in 17.4% of all resistance cases (4/27) and 3.2% of relapses (2/63). Half of patients switched completely from BCP-ALL to CD19-negative acute myeloid leukemia, others retained CD19-positive B-blasts and acquired an additional CD19-negative blast population: myeloid or unclassifiable. Five patients had KMT2A gene rearrangements; one had TCF3::ZNF384 translocation. The presented cases showed consistency of gene rearrangements and fusion transcripts across initially diagnosed leukemia and lineage switch. In two of six patients, the clonal architecture assessed by IG/TR gene rearrangements was stable, while in others, loss of clones or gain of new clones was noted. KMT2A-r patients demonstrated very few additional mutations, while in the TCF3::ZNF384 case, lineage switch was accompanied by a large set of additional mutations. The immunophenotype of an existing leukemia sometimes changes via different mechanisms and with different additional molecular changes. Careful investigation of all BM compartments together with all molecular –minimal residual disease studies can lead to reliable identification of lineage switch. MDPI 2022-04-05 /pmc/articles/PMC8999738/ /pubmed/35409391 http://dx.doi.org/10.3390/ijms23074019 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Semchenkova, Alexandra Mikhailova, Ekaterina Komkov, Alexander Gaskova, Marina Abasov, Ruslan Matveev, Evgenii Kazanov, Marat Mamedov, Ilgar Shmitko, Anna Belova, Vera Miroshnichenkova, Anna Illarionova, Olga Olshanskaya, Yulia Tsaur, Grigory Verzhbitskaya, Tatiana Ponomareva, Natalia Bronin, Gleb Kondratchik, Konstantin Fechina, Larisa Diakonova, Yulia Vavilova, Liudmila Myakova, Natalia Novichkova, Galina Maschan, Alexey Maschan, Michael Zerkalenkova, Elena Popov, Alexander Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title | Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title_full | Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title_fullStr | Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title_full_unstemmed | Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title_short | Lineage Conversion in Pediatric B-Cell Precursor Acute Leukemia under Blinatumomab Therapy |
title_sort | lineage conversion in pediatric b-cell precursor acute leukemia under blinatumomab therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999738/ https://www.ncbi.nlm.nih.gov/pubmed/35409391 http://dx.doi.org/10.3390/ijms23074019 |
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