<i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol
In this study, we aimed to identify patients within our B-ALL cohort with altered <i>PAX5</i>. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/6/1164 |
| _version_ | 1797241714462687232 |
|---|---|
| author | Klementina Črepinšek Nika Klobučar Tine Tesovnik Robert Šket Barbara Jenko Bizjan Jernej Kovač Marko Kavčič Tomaž Prelog Lidija Kitanovski Janez Jazbec Maruša Debeljak |
| author_facet | Klementina Črepinšek Nika Klobučar Tine Tesovnik Robert Šket Barbara Jenko Bizjan Jernej Kovač Marko Kavčič Tomaž Prelog Lidija Kitanovski Janez Jazbec Maruša Debeljak |
| author_sort | Klementina Črepinšek |
| collection | DOAJ |
| description | In this study, we aimed to identify patients within our B-ALL cohort with altered <i>PAX5</i>. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children’s Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. <i>PAX5</i> was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a <i>PAX5</i>-associated genetic subtype that were previously classified as “B-other”, and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in <i>PAX5</i> compared to other hyperdiploid cases. We also report an interesting case of a patient with <i>PAX5::FKBP15</i> and a pathogenic variant in <i>PTPN11</i> who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse <i>PAX5</i> alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes. |
| first_indexed | 2024-04-24T18:27:43Z |
| format | Article |
| id | doaj.art-33e7d71e327844b0813a697d7174f83b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-24T18:27:43Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-33e7d71e327844b0813a697d7174f83b2024-03-27T13:30:00ZengMDPI AGCancers2072-66942024-03-01166116410.3390/cancers16061164<i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 ProtocolKlementina Črepinšek0Nika Klobučar1Tine Tesovnik2Robert Šket3Barbara Jenko Bizjan4Jernej Kovač5Marko Kavčič6Tomaž Prelog7Lidija Kitanovski8Janez Jazbec9Maruša Debeljak10Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaDepartment of Oncology and Haematology, University Children’s Hospital, University Medical Centre Ljubljana, Bohoričeva ulica 20, 1000 Ljubljana, SloveniaDepartment of Oncology and Haematology, University Children’s Hospital, University Medical Centre Ljubljana, Bohoričeva ulica 20, 1000 Ljubljana, SloveniaDepartment of Oncology and Haematology, University Children’s Hospital, University Medical Centre Ljubljana, Bohoričeva ulica 20, 1000 Ljubljana, SloveniaDepartment of Oncology and Haematology, University Children’s Hospital, University Medical Centre Ljubljana, Bohoričeva ulica 20, 1000 Ljubljana, SloveniaClinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, SloveniaIn this study, we aimed to identify patients within our B-ALL cohort with altered <i>PAX5</i>. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children’s Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. <i>PAX5</i> was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a <i>PAX5</i>-associated genetic subtype that were previously classified as “B-other”, and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in <i>PAX5</i> compared to other hyperdiploid cases. We also report an interesting case of a patient with <i>PAX5::FKBP15</i> and a pathogenic variant in <i>PTPN11</i> who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse <i>PAX5</i> alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.https://www.mdpi.com/2072-6694/16/6/1164childhood B-cell acute lymphoblastic leukemia<i>PAX5</i> genetic alterationsprognostic significance |
| spellingShingle | Klementina Črepinšek Nika Klobučar Tine Tesovnik Robert Šket Barbara Jenko Bizjan Jernej Kovač Marko Kavčič Tomaž Prelog Lidija Kitanovski Janez Jazbec Maruša Debeljak <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol Cancers childhood B-cell acute lymphoblastic leukemia <i>PAX5</i> genetic alterations prognostic significance |
| title | <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol |
| title_full | <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol |
| title_fullStr | <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol |
| title_full_unstemmed | <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol |
| title_short | <i>PAX5</i> Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol |
| title_sort | i pax5 i alterations in a consecutive childhood b cell acute lymphoblastic leukemia cohort treated using the all ic bfm 2009 protocol |
| topic | childhood B-cell acute lymphoblastic leukemia <i>PAX5</i> genetic alterations prognostic significance |
| url | https://www.mdpi.com/2072-6694/16/6/1164 |
| work_keys_str_mv | AT klementinacrepinsek ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT nikaklobucar ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT tinetesovnik ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT robertsket ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT barbarajenkobizjan ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT jernejkovac ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT markokavcic ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT tomazprelog ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT lidijakitanovski ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT janezjazbec ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol AT marusadebeljak ipax5ialterationsinaconsecutivechildhoodbcellacutelymphoblasticleukemiacohorttreatedusingtheallicbfm2009protocol |