Clinical impact of NOTCH1 and/or FBXW7 mutations, FLASH deletion, and TCR status in pediatric T-cell lymphoblastic lymphoma.
Celine Callens
(1)
,
Frederic Baleydier
(2, 3)
,
Etienne Lengline
(4)
,
Raouf Ben Abdelali
(5)
,
Arnaud Petit
(6)
,
Patrick Villarese
(7)
,
Agata Cieslak
(7)
,
Veronique Minard-Colin
(8)
,
Anne Rullier
(9)
,
Anne Moreau
(10)
,
André Baruchel
(11, 12)
,
Claudine Schmitt
(13)
,
Vahid Asnafi
(14)
,
Yves Bertrand
(3)
,
Elizabeth Macintyre
(15)
1
CHRI -
Cytokines, hématopoïèse et réponse immune
2 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
3 Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL]
4 CIC-BT 502 - CIC - Biotherapie - GHU Ouest APHP
5 Hôpital Necker - Enfants Malades [AP-HP]
6 CHU Trousseau [APHP]
7 ERL 8254 - Equipe Inserm U1163 - Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications
8 Department of Immunology
9 Laboratoire d'anatomie pathologique
10 LMA [Poitiers] - Laboratoire de mathématiques et applications [UMR 6086]
11 Hôpital Robert Debré Paris
12 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
13 Service d'Hématologie Pédiatrique [CHRU Nancy]
14 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
15 Service hématologie
2 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
3 Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL]
4 CIC-BT 502 - CIC - Biotherapie - GHU Ouest APHP
5 Hôpital Necker - Enfants Malades [AP-HP]
6 CHU Trousseau [APHP]
7 ERL 8254 - Equipe Inserm U1163 - Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications
8 Department of Immunology
9 Laboratoire d'anatomie pathologique
10 LMA [Poitiers] - Laboratoire de mathématiques et applications [UMR 6086]
11 Hôpital Robert Debré Paris
12 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
13 Service d'Hématologie Pédiatrique [CHRU Nancy]
14 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
15 Service hématologie
Arnaud Petit
- Fonction : Auteur
- PersonId : 1903
- IdHAL : arnaudpetit
- ORCID : 0000-0001-8363-1622
- IdRef : 087801582
Agata Cieslak
- Fonction : Auteur
- PersonId : 771771
- ORCID : 0000-0003-1015-9448
Anne Moreau
- Fonction : Auteur
- PersonId : 1202589
Yves Bertrand
- Fonction : Auteur
- PersonId : 854932
Elizabeth Macintyre
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 902525
Connectez-vous pour contacter l'auteur
Résumé
PURPOSE: Pediatric T-cell lymphoblastic lymphomas (T-LBL) are commonly treated on T-cell acute lymphoblastic leukemia (T-ALL) -derived protocols. Therapeutic stratification based on response to the prephase treatment and on minimal residual disease assessment is well established in T-ALL but is not easy to extrapolate to T-LBL. The identification of molecular prognostic markers at diagnosis in T-LBL could provide an alternative for early therapeutic stratification. Our study determines the frequency and prognostic value of NOTCH1/FBXW7 mutations (N/F(mut)), FLASH deletion at chromosome 6q, and TCR rearrangements in a prospective cohort of pediatric T-LBL. PATIENTS AND METHODS: Pathologic samples were obtained at diagnosis for 54 patients treated according to the EuroLB02 protocol in France. N/F(mut) were identified by direct sequencing and allelic dosage was used to detect FLASH and TCRγ deletions, which were interpreted in conjunction with TCRγ, TCRβ, and TCRδ rearrangements. RESULTS: N/F(mut) were found in 55% of T-LBL patients, in whom they were associated with improved event-free survival (P < .01) and overall survival (P < .01). FLASH monoallelic deletions were observed in 18% of patients; they were predominantly N/F wild-type (six of nine) and tended to be of inferior prognosis (P = .09). Absence of biallelic TCRγ deletion (ABD) was seen in 7%, all of which were N/F(mut) and identified a poor prognosis group (P = .02). On multivariate analysis of N/F(mut), TCRγ ABD, and FLASH deletion, only N/F(mut) was an independent factor for good prognosis. CONCLUSION: Mutational status of NOTCH1/FBXW7 represents a promising marker for early therapeutic stratification in pediatric T-LBL.
Domaines
CancerFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Clinical impact of NOTCH1 and/or FBXW7 mutations, FLASH deletion, and TCR status in pediatric T-cell lymphoblastic lymphoma.
|
Résumé |
en
PURPOSE: Pediatric T-cell lymphoblastic lymphomas (T-LBL) are commonly treated on T-cell acute lymphoblastic leukemia (T-ALL) -derived protocols. Therapeutic stratification based on response to the prephase treatment and on minimal residual disease assessment is well established in T-ALL but is not easy to extrapolate to T-LBL. The identification of molecular prognostic markers at diagnosis in T-LBL could provide an alternative for early therapeutic stratification. Our study determines the frequency and prognostic value of NOTCH1/FBXW7 mutations (N/F(mut)), FLASH deletion at chromosome 6q, and TCR rearrangements in a prospective cohort of pediatric T-LBL. PATIENTS AND METHODS: Pathologic samples were obtained at diagnosis for 54 patients treated according to the EuroLB02 protocol in France. N/F(mut) were identified by direct sequencing and allelic dosage was used to detect FLASH and TCRγ deletions, which were interpreted in conjunction with TCRγ, TCRβ, and TCRδ rearrangements. RESULTS: N/F(mut) were found in 55% of T-LBL patients, in whom they were associated with improved event-free survival (P < .01) and overall survival (P < .01). FLASH monoallelic deletions were observed in 18% of patients; they were predominantly N/F wild-type (six of nine) and tended to be of inferior prognosis (P = .09). Absence of biallelic TCRγ deletion (ABD) was seen in 7%, all of which were N/F(mut) and identified a poor prognosis group (P = .02). On multivariate analysis of N/F(mut), TCRγ ABD, and FLASH deletion, only N/F(mut) was an independent factor for good prognosis. CONCLUSION: Mutational status of NOTCH1/FBXW7 represents a promising marker for early therapeutic stratification in pediatric T-LBL.
|
Auteur(s) |
Celine Callens
1
, Frederic Baleydier
2, 3
, Etienne Lengline
4
, Raouf Ben Abdelali
5
, Arnaud Petit
6
, Patrick Villarese
7
, Agata Cieslak
7
, Veronique Minard-Colin
8
, Anne Rullier
9
, Anne Moreau
10
, André Baruchel
11, 12
, Claudine Schmitt
13
, Vahid Asnafi
14
, Yves Bertrand
3
, Elizabeth Macintyre
15
1
CHRI -
Cytokines, hématopoïèse et réponse immune
( 1288 )
- Bâtiment Sèvres - Porte I
161 Rue de Sèvres
75743 PARIS CEDEX 15
- France
2
UNICANCER/CRCL -
Centre de Recherche en Cancérologie de Lyon
( 139829 )
- 28, rue Laennec - 69373 Lyon
- France
3
Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL]
( 133668 )
- Hôpital Lyon-Sud
Chemin du Grand Revoyet
69495 Pierre-Bénite
- France
4
CIC-BT 502 -
CIC - Biotherapie - GHU Ouest APHP
( 2590 )
- Faculté de Médecine - 156 Rue de Vaugirard 75015 Paris
- France
5
Hôpital Necker - Enfants Malades [AP-HP]
( 414766 )
- 149 Rue de Sèvres 75015 Paris
- France
6
CHU Trousseau [APHP]
( 360410 )
- 26 Avenue du Dr Arnold Netter, 75012 Paris
- France
7
ERL 8254 - Equipe Inserm U1163 -
Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications
( 88548 )
- 24, Boulevard de Montparnasse
75015 PARIS
- France
8
Department of Immunology
( 107406 )
- Durham, North Carolina
- États-Unis
9
Laboratoire d'anatomie pathologique
( 55761 )
- France
10
LMA [Poitiers] -
Laboratoire de mathématiques et applications [UMR 6086]
( 68 )
- Téléport 2 – BP 30179 – Boulevard Marie et Pierre Curie – 86962 Futuroscope Chasseneuil Cedex – France
- Namibie
11
Hôpital Robert Debré Paris
( 116327 )
- Hôpital Robert Debré, service ORL, 48 Boulevard Sérurier, 75019 Paris
- France
12
Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
( 212052 )
- France
13
Service d'Hématologie Pédiatrique [CHRU Nancy]
( 18102 )
- Nancy
- France
14
IMAGINE - U1163 -
Imagine - Institut des maladies génétiques
( 247401 )
- IHU Imagine,
156 rue de Vaugirard, 75015 PARIS
et
24 Boulevard du Montparnasse, 75015 Paris
- France
15
Service hématologie
( 202761 )
- 149 rue de Sèvres 75015 Paris
- France
|
Comité de lecture |
Oui
|
Vulgarisation |
Non
|
Langue du document |
Anglais
|
Nom de la revue |
|
Audience |
Internationale
|
Date de publication |
2012-06-01
|
Date de publication électronique |
2012-04-30
|
Volume |
30
|
Numéro |
16
|
Page/Identifiant |
1966-73
|
Domaine(s) |
|
Mots-clés (Mesh) |
|
DOI | 10.1200/JCO.2011.39.7661 |
Pubmed Id | 22547598 |
Loading...