NOTCH1 fusion genes in pediatric T-cell lymphoblastic lymphoma hallmark a common high-risk subgroup with blood TARC levels as possible diagnostic biomarker
Abstract Background Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to proactively recognize these high-risk T-LBL patients through identification of specific molecular characteristics and generic biomarkers.Patients and Methods In 29/43 unselected pediatric T-LBL patients diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018-2023, RNA sequencing was performed at diagnosis, and blood thymus and activation-regulated chemokine (TARC) levels were measured at diagnosis in 22/29 patients.Results We discovered a previously unknown high-risk biological subgroup of children with T-LBL, characterized byNOTCH1gene fusions, which was found in 21% of our T-LBL cohort (6/29). All patients presented uniformly with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Moreover, all six patients exclusively expressed highly elevated blood TARC levels, defining a novel and previously not known clinically relevant blood biomarker for T-cell lymphoblastic lymphoma. Three out of these six patients relapsed during therapy, while a fourth developed a therapy related acute myeloid leukemia during maintenance therapy.Conclusion We identified a frequently occurring T-LBL entity with high risk of relapse which can be easily identified using a blood TARC screening at diagnosis. Further molecular characterization throughNOTCH1gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 06. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kroeze, Emma [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.31.24301517 |
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| PPN (Katalog-ID): |
XBI04237815X |
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| 520 | |a Abstract Background Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to proactively recognize these high-risk T-LBL patients through identification of specific molecular characteristics and generic biomarkers.Patients and Methods In 29/43 unselected pediatric T-LBL patients diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018-2023, RNA sequencing was performed at diagnosis, and blood thymus and activation-regulated chemokine (TARC) levels were measured at diagnosis in 22/29 patients.Results We discovered a previously unknown high-risk biological subgroup of children with T-LBL, characterized byNOTCH1gene fusions, which was found in 21% of our T-LBL cohort (6/29). All patients presented uniformly with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Moreover, all six patients exclusively expressed highly elevated blood TARC levels, defining a novel and previously not known clinically relevant blood biomarker for T-cell lymphoblastic lymphoma. Three out of these six patients relapsed during therapy, while a fourth developed a therapy related acute myeloid leukemia during maintenance therapy.Conclusion We identified a frequently occurring T-LBL entity with high risk of relapse which can be easily identified using a blood TARC screening at diagnosis. Further molecular characterization throughNOTCH1gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies. | ||
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| 700 | 1 | |a Kleisman, Michelle M |4 aut | |
| 700 | 1 | |a Kester, Lennart A |0 (orcid)0000-0002-8259-9971 |4 aut | |
| 700 | 1 | |a Scheijde-Vermeulen, Marijn A |0 (orcid)0000-0001-8926-1140 |4 aut | |
| 700 | 1 | |a Sonneveld, Edwin |0 (orcid)0000-0002-1869-0957 |4 aut | |
| 700 | 1 | |a Buijs-Gladdines, Jessica GC |4 aut | |
| 700 | 1 | |a Hagleitner, Melanie M |0 (orcid)0000-0001-9424-0352 |4 aut | |
| 700 | 1 | |a Meyer-Wentrup, Friederike AG |0 (orcid)0000-0002-6277-1973 |4 aut | |
| 700 | 1 | |a Veening, Margreet A |0 (orcid)0000-0001-9503-0795 |4 aut | |
| 700 | 1 | |a Beishuizen, Auke |0 (orcid)0000-0002-6482-1823 |4 aut | |
| 700 | 1 | |a Meijerink, Jules PP |0 (orcid)0000-0002-6860-798X |4 aut | |
| 700 | 1 | |a Loeffen, Jan LC |0 (orcid)0000-0002-2537-5779 |4 aut | |
| 700 | 1 | |a Kuiper, Roland P |0 (orcid)0000-0003-4928-3809 |4 aut | |
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