Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion
Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemi...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Pathology and Oncology Research |
| Subjects: | |
| Online Access: | https://www.por-journal.com/articles/10.3389/pore.2022.1610570/full |
| _version_ | 1797220981228437504 |
|---|---|
| author | Egle Stukaite-Ruibiene Rimvydas Norvilas Rimvydas Norvilas Vaidas Dirse Sigita Stankeviciene Goda Elizabeta Vaitkeviciene Goda Elizabeta Vaitkeviciene |
| author_facet | Egle Stukaite-Ruibiene Rimvydas Norvilas Rimvydas Norvilas Vaidas Dirse Sigita Stankeviciene Goda Elizabeta Vaitkeviciene Goda Elizabeta Vaitkeviciene |
| author_sort | Egle Stukaite-Ruibiene |
| collection | DOAJ |
| description | Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic NUP214::ABL1 fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected NUP214::ABL1 gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant ABL1 mutations; therefore, treatment with Imatinib was added to target the NUP214::ABL1 fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase. |
| first_indexed | 2024-04-24T12:58:10Z |
| format | Article |
| id | doaj.art-00a6120b7306425192ee15a1d80d6ea6 |
| institution | Directory Open Access Journal |
| issn | 1532-2807 |
| language | English |
| last_indexed | 2024-04-24T12:58:10Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Pathology and Oncology Research |
| spelling | doaj.art-00a6120b7306425192ee15a1d80d6ea62024-04-05T16:24:45ZengFrontiers Media S.A.Pathology and Oncology Research1532-28072022-09-012810.3389/pore.2022.16105701610570Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene FusionEgle Stukaite-Ruibiene0Rimvydas Norvilas1Rimvydas Norvilas2Vaidas Dirse3Sigita Stankeviciene4Goda Elizabeta Vaitkeviciene5Goda Elizabeta Vaitkeviciene6Faculty of Medicine, Vilnius University, Vilnius, LithuaniaHematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaDepartment of Experimental, Preventive and Clinical Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, LithuaniaHematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaCenter for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaFaculty of Medicine, Vilnius University, Vilnius, LithuaniaCenter for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius, LithuaniaAcute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic NUP214::ABL1 fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected NUP214::ABL1 gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant ABL1 mutations; therefore, treatment with Imatinib was added to target the NUP214::ABL1 fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase.https://www.por-journal.com/articles/10.3389/pore.2022.1610570/fullcase reporttargeted therapytyrosine kinase inhibitorsacute lymphoblastic leukemiaimatinibBCR-ABL1-like |
| spellingShingle | Egle Stukaite-Ruibiene Rimvydas Norvilas Rimvydas Norvilas Vaidas Dirse Sigita Stankeviciene Goda Elizabeta Vaitkeviciene Goda Elizabeta Vaitkeviciene Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion Pathology and Oncology Research case report targeted therapy tyrosine kinase inhibitors acute lymphoblastic leukemia imatinib BCR-ABL1-like |
| title | Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion |
| title_full | Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion |
| title_fullStr | Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion |
| title_full_unstemmed | Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion |
| title_short | Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion |
| title_sort | case report specific abl inhibitor imatinib is an effective targeted agent as the first line therapy to treat b cell acute lymphoblastic leukemia with a cryptic nup214 abl1 gene fusion |
| topic | case report targeted therapy tyrosine kinase inhibitors acute lymphoblastic leukemia imatinib BCR-ABL1-like |
| url | https://www.por-journal.com/articles/10.3389/pore.2022.1610570/full |
| work_keys_str_mv | AT eglestukaiteruibiene casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT rimvydasnorvilas casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT rimvydasnorvilas casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT vaidasdirse casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT sigitastankeviciene casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT godaelizabetavaitkeviciene casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion AT godaelizabetavaitkeviciene casereportspecificablinhibitorimatinibisaneffectivetargetedagentasthefirstlinetherapytotreatbcellacutelymphoblasticleukemiawithacrypticnup214abl1genefusion |