SET-NUP214 is a recurrent γδ lineage-specific fusion transcript associated with corticosteroid/chemotherapy resistance in adult T-ALL.
The SET-NUP214 (TAF1/CAN) fusion gene is a rare genetic event in T-cell acute lymphoblastic leukemia (T-ALL). Eleven (6%) of 196 T-ALL patients enrolled in the French Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) 2003 and 2005 trials harbored a SET-NUP214 transcript. SET-NUP214-positive patients were predominantly (10 [91%] of 11) T-cell receptor (TCR)-negative and strikingly associated with TCRγδ lineage T-ALLs, as defined by expression of TCRγδ, TCRδ and/or TCRγ rearrangements but no complete TCRβ variable diversity joining rearrangement in surface CD3/TCR-negative cases. When compared with SET-NUP214-negative patients, SET-NUP214-positive patients showed a significantly higher rate of corticosteroid resistance (91% vs 44%; P = .003) and chemotherapy resistance (100% vs 44%; P = .0001). All SET-NUP214-positive patients but one achieved complete remission, and 9 were allografted. Despite the poor early-treatment sensitivity, the outcome of SET-NUP214-positive patients was similar to that of SET-NUP214-negative patients.
Université de Médecine Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France;
Raouf
R
Ben Abdelali
Anne
A
Roggy
Thibaut
T
Leguay
Agata
A
Cieslak
Aline
A
Renneville
Aurore
A
Touzart
Anne
A
Banos
Edouard
E
Randriamalala
Denis
D
Caillot
Bruno
B
Lioure
Alain
A
Devidas
Hossein
H
Mossafa
Claude
C
Preudhomme
Norbert
N
Ifrah
Hervé
H
Dombret
Elizabeth
E
Macintyre
Vahid
V
Asnafi
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D056488:Histone Chaperones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D050596:Oncogene Fusion; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C513473:SET protein, human; D014157:Transcription Factors