Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.
Amélie Trinquand
,
Aline Tanguy-Schmidt
,
Raouf Ben Abdelali
,
Jérôme Lambert
,
Kheira Beldjord
,
Etienne Lengliné
,
Noémie de Gunzburg
,
Dominique Payet-Bornet
(1)
,
Ludovic Lhermitte
,
Hossein Mossafa
(2)
,
Véronique Lhéritier
,
Jonathan Bond
,
Françoise Huguet
(3)
,
Agnès Buzyn
(4)
,
Thibaud Leguay
,
Jean-Yves Cahn
(5)
,
Xavier Thomas
(6, 7)
,
Yves Chalandon
,
André Delannoy
(8)
,
Caroline Bonmati
,
Sebastien Maury
,
Bertrand Nadel
(1)
,
Elizabeth Macintyre
(9)
,
Norbert Ifrah
(10)
,
Hervé Dombret
(11)
,
Vahid Asnafi
(12)
1
CIML -
Centre d'Immunologie de Marseille - Luminy
2 Laboratoire de Cytogénétique - Pasteur-Cerba
3 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
4 UMR_S567 / UMR 8104 - Institut Cochin
5 TheREx
6 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
7 Hôpital Edouard Herriot [CHU - HCL]
8 Hôpital de Jolimont
9 Service hématologie
10 Service d'hématologie clinique [Avicenne]
11 Lymphocyte et cancer
12 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
2 Laboratoire de Cytogénétique - Pasteur-Cerba
3 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
4 UMR_S567 / UMR 8104 - Institut Cochin
5 TheREx
6 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
7 Hôpital Edouard Herriot [CHU - HCL]
8 Hôpital de Jolimont
9 Service hématologie
10 Service d'hématologie clinique [Avicenne]
11 Lymphocyte et cancer
12 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
Amélie Trinquand
- Fonction : Auteur
Aline Tanguy-Schmidt
- Fonction : Auteur
- PersonId : 749561
- IdHAL : aline-schmidt
- ORCID : 0000-0003-0278-7479
Raouf Ben Abdelali
- Fonction : Auteur
Jérôme Lambert
- Fonction : Auteur
Kheira Beldjord
- Fonction : Auteur
Etienne Lengliné
- Fonction : Auteur
Noémie de Gunzburg
- Fonction : Auteur
Dominique Payet-Bornet
- Fonction : Auteur
- PersonId : 741466
- IdHAL : dominique-payet
- ORCID : 0000-0003-3196-3814
- IdRef : 161208843
Ludovic Lhermitte
- Fonction : Auteur
- PersonId : 771345
- ORCID : 0000-0003-2498-0376
Véronique Lhéritier
- Fonction : Auteur
Jonathan Bond
- Fonction : Auteur
Thibaud Leguay
- Fonction : Auteur
Yves Chalandon
- Fonction : Auteur
- PersonId : 767676
- ORCID : 0000-0001-9341-8104
Caroline Bonmati
- Fonction : Auteur
Sebastien Maury
- Fonction : Auteur
Elizabeth Macintyre
- Fonction : Auteur
- PersonId : 762165
- ORCID : 0000-0003-0520-0493
Résumé
PURPOSE: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. PATIENTS AND METHODS: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). RESULTS: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). CONCLUSION: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Domaines
Immunité innéeFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.
|
Résumé |
en
PURPOSE: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. PATIENTS AND METHODS: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). RESULTS: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). CONCLUSION: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
|
Auteur(s) |
Amélie Trinquand
, Aline Tanguy-Schmidt
, Raouf Ben Abdelali
, Jérôme Lambert
, Kheira Beldjord
, Etienne Lengliné
, Noémie de Gunzburg
, Dominique Payet-Bornet
1
, Ludovic Lhermitte
, Hossein Mossafa
2
, Véronique Lhéritier
, Jonathan Bond
, Françoise Huguet
3
, Agnès Buzyn
4
, Thibaud Leguay
, Jean-Yves Cahn
5
, Xavier Thomas
6, 7
, Yves Chalandon
, André Delannoy
8
, Caroline Bonmati
, Sebastien Maury
, Bertrand Nadel
1
, Elizabeth Macintyre
9
, Norbert Ifrah
10
, Hervé Dombret
11
, Vahid Asnafi
12
1
CIML -
Centre d'Immunologie de Marseille - Luminy
( 182245 )
- Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09
- France
2
Laboratoire de Cytogénétique - Pasteur-Cerba
( 82510 )
- France
3
Service Hématologie - IUCT-Oncopole [CHU Toulouse]
( 518500 )
- Institut Universitaire du Cancer de Toulouse - Oncopole,
1, avenue Irène Joliot-Curie - 31059 Toulouse cedex 9
- France
4
UMR_S567 / UMR 8104 -
Institut Cochin
( 1249 )
- Bâtiment MECHAIN 22 rue Méchain 75014 PARIS
- France
5
TheREx
( 388270 )
-
- France
6
UNICANCER/CRCL -
Centre de Recherche en Cancérologie de Lyon
( 139829 )
- 28, rue Laennec - 69373 Lyon
- France
7
Hôpital Edouard Herriot [CHU - HCL]
( 300094 )
- 5 Place d'Arsonval
69003 Lyon
- France
8
Hôpital de Jolimont
( 165417 )
- Brussels
- Belgique
9
Service hématologie
( 202761 )
- 149 rue de Sèvres 75015 Paris
- France
10
Service d'hématologie clinique [Avicenne]
( 99728 )
- 125, rue de Stalingrad 93000 Bobigny
- France
11
Lymphocyte et cancer
( 58157 )
- Hopital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris
- France
12
IMAGINE - U1163 -
Imagine - Institut des maladies génétiques
( 247401 )
- IHU Imagine,
156 rue de Vaugirard, 75015 PARIS
et
24 Boulevard du Montparnasse, 75015 Paris
- France
|
Comité de lecture |
Oui
|
Vulgarisation |
Non
|
Langue du document |
Anglais
|
Nom de la revue |
|
Audience |
Internationale
|
Date de publication |
2013-12-01
|
Date de publication électronique |
2013-10-28
|
Volume |
31
|
Numéro |
34
|
Page/Identifiant |
4333-42
|
Domaine(s) |
|
Mots-clés (Mesh) |
|
DOI | 10.1200/JCO.2012.48.5292 |
Pubmed Id | 24166518 |
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