title: The prognosis of CALM-AF10-positive adult T-cell acute lymphoblastic leukemias depends on the stage of maturation arrest.
abstract: CALM-AF10 (also known as PICALM-MLLT10) is the commonest fusion protein in T-cell acute lymphoblastic leukemia, but its prognostic impact remains unclear. Molecular screening at diagnosis identified CALM-AF10 in 30/431 (7%) patients with T-cell acute lymphoblastic leukemia aged 16 years and over and in 15/234 (6%) of those aged up to 15 years. Adult CALM-AF10-positive patients were predominantly (72%) negative for surface (s)CD3/T-cell receptor, whereas children were predominantly (67%) positive for T-cell receptor. Among 22 adult CALM-AF10-positive patients treated according to the LALA94/GRAALL03-05 protocols, the poor prognosis for event-free survival (P=0.0017) and overall survival (P=0.0014) was restricted to the 15 T-cell receptor-negative cases. Among CALM-AF10-positive, T-cell receptor-negative patients, 82% had an early T-cell precursor phenotype, reported to be of poor prognosis in pediatric T-cell acute lymphoblastic leukemia. Early T-cell precursor acute lymphoblastic leukemia corresponded to 22% of adult LALA94/GRAALL03-05 T-cell acute lymphoblastic leukemias, but had no prognostic impact per se. CALM-AF10 fusion within early T-cell precursor acute lymphoblastic leukemia (21%) did, however, identify a group with a poor prognosis with regards to event-free survival (P=0.04). CALM-AF10 therefore identifies a poor prognostic group within sCD3/T-cell receptor negative adult T-cell acute lymphoblastic leukemias and is over-represented within early T-cell precursor acute lymphoblastic leukemias, in which it identifies patients in whom treatment is likely to fail. Its prognosis and overlap with early T-cell precursor acute lymphoblastic leukemia in pediatric T-cell acute lymphoblastic leukemia merits analysis. The clinical trial GRAALL was registered at Clinical Trials.gov number NCT00327678.
authors.affiliation: elizabeth.macintyre@nck.aphp.fr.
authors.forename: Raouf
authors.initials: R
authors.lastname: Ben Abdelali
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Petit
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Micol
authors.forename: Céline
authors.initials: C
authors.lastname: Callens
authors.forename: Patrick
authors.initials: P
authors.lastname: Villarese
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Stephane
authors.initials: S
authors.lastname: Lepretre
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.forename: Gaelle
authors.initials: G
authors.lastname: Guillerm
authors.forename: Céline
authors.initials: C
authors.lastname: Berthon
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.forename: Bernadette
authors.initials: B
authors.lastname: Corront
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Béné
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C092513:MLLT10 protein, human; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D014157:Transcription Factors