Abstract

T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.

Details

Title
Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
Author
Steimlé, Thomas 1 ; Marie-Emilie, Dourthe 2 ; Alcantara, Marion 3   VIAFID ORCID Logo  ; Touzart Aurore 4 ; Simonin Mathieu 5 ; Mondesir Johanna 6 ; Lhermitte Ludovic 6   VIAFID ORCID Logo  ; Bond, Jonathan 7 ; Graux Carlos 8 ; Grardel Nathalie 9 ; Jean-Michel, Cayuela 10 ; Arnoux, Isabelle 11 ; Gandemer Virginie 12 ; Balsat Marie 13 ; Vey Norbert 14   VIAFID ORCID Logo  ; Macintyre, Elizabeth 15   VIAFID ORCID Logo  ; Ifrah Norbert 16 ; Dombret Hervé 17 ; Petit Arnaud 18   VIAFID ORCID Logo  ; Baruchel André 19 ; Ruminy Philippe 20 ; Boissel, Nicolas 21 ; Asnafi Vahid 22   VIAFID ORCID Logo 

1  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France 
2  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France; Robert Debré University Hospital (AP-HP), Université de Paris, Department of Pediatric Hematology and Immunology, Paris, France 
3  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France; Robert Debré University Hospital (AP-HP), Université de Paris, Department of Pediatric Hematology and Immunology, Paris, France; Institut Curie, PSL Research University, Center for Cancer Immunotherapy, INSERM U932, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384) 
4  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France (GRID:grid.418596.7) 
5  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France (GRID:grid.418596.7); Robert Debré University Hospital (AP-HP), Université de Paris, Department of Pediatric Hematology and Immunology, Paris, France (GRID:grid.418596.7); Institut Curie, PSL Research University, Center for Cancer Immunotherapy, INSERM U932, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384); Assistance Publique-Hôpitaux de Paris (AP-HP), GH HUEP, Armand Trousseau Hospital, Department of Pediatric Hematology and Oncology, Paris, France (GRID:grid.413776.0) (ISNI:0000 0004 1937 1098); Sorbonne Universités, UPMC Univ Paris 06, UMRS 938, CDR Saint-Antoine, GRC n°07, GRC MyPAC, Paris, France (GRID:grid.465261.2) (ISNI:0000 0004 1793 5929) 
6  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France (GRID:grid.465261.2) 
7  University College Dublin, Systems Biology Ireland, School of Medicine, Dublin, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743) 
8  Université catholique de Louvain, CHU UCL Namur - site Godinne, Department of Hematology, Yvoir, Belgium (GRID:grid.7942.8) (ISNI:0000 0001 2294 713X) 
9  CHRU Lille, Lille, France and U1172, INSERM, Laboratory of Hematology, Lille, France (GRID:grid.410463.4) (ISNI:0000 0004 0471 8845) 
10  Laboratory of Hematology and EA 3518 University Hospital Saint-Louis, AP-HP and Université de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602) 
11  Marseille University Hospital Timone, Hematology Laboratory, Marseille, France (GRID:grid.414336.7) (ISNI:0000 0001 0407 1584) 
12  University Hospital of Rennes, Department of Pediatric Hematology and Oncology, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984) 
13  Service d’hématologie clinique, Hôpital Lyon Sud, Marseille, France (GRID:grid.411430.3) (ISNI:0000 0001 0288 2594) 
14  Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France (GRID:grid.463833.9) (ISNI:0000 0004 0572 0656) 
15  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France (GRID:grid.463833.9) 
16  PRES LUNAM, CHU Angers service des Maladies du Sang et CRCINA INSERM, Angers, France (GRID:grid.411147.6) (ISNI:0000 0004 0472 0283) 
17  Institut de Recherche Saint-Louis, Université de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602) 
18  Assistance Publique-Hôpitaux de Paris (AP-HP), GH HUEP, Armand Trousseau Hospital, Department of Pediatric Hematology and Oncology, Paris, France (GRID:grid.413776.0) (ISNI:0000 0004 1937 1098); Sorbonne Universités, UPMC Univ Paris 06, UMRS 938, CDR Saint-Antoine, GRC n°07, GRC MyPAC, Paris, France (GRID:grid.465261.2) (ISNI:0000 0004 1793 5929) 
19  Robert Debré University Hospital (AP-HP), Université de Paris, Department of Pediatric Hematology and Immunology, Paris, France (GRID:grid.465261.2); Institut de Recherche Saint-Louis, Université de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602) 
20  Inserm U1245, Centre Henri Becquerel, Université de Rouen, IRIB, Rouen, France (GRID:grid.10400.35) (ISNI:0000 0001 2108 3034) 
21  Institut de Recherche Saint-Louis, Université de Paris, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Inserm U1245, Centre Henri Becquerel, Université de Rouen, IRIB, Rouen, France (GRID:grid.10400.35) (ISNI:0000 0001 2108 3034); AP-HP, Hôpital Saint Louis, Unité d’Hématologie Adolescents et Jeunes Adultes, Paris, France (GRID:grid.413328.f) (ISNI:0000 0001 2300 6614) 
22  Université de Paris (Descartes), Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France (GRID:grid.413328.f) 
Publication year
2022
Publication date
Jan 2022
Publisher
Springer Nature B.V.
e-ISSN
20445385
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41408-022-00613-9
ProQuest document ID
2622858639
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.