Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway.

Palmi, C., Savino, A., Silvestri, D., Bronzini, I., Cario, G., Paganin, M., et al. (2016). CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia. ONCOTARGET, 7(37), 59260-59272 [10.18632/oncotarget.10610].

CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

PALMI, CHIARA
Primo
;
SAVINO, ANGELA MARIA
Secondo
;
VILLA, ANTONELLO;GAIPA, GIUSEPPE;BIONDI, ANDREA;VALSECCHI, MARIA GRAZIA;CONTER, VALENTINO;CAZZANIGA, GIOVANNI ITALO
2016

Abstract

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway.
Si
Articolo in rivista - Articolo scientifico
Scientifica
CRLF2; High risk; Pediatric leukemia; Prognostic marker; T acute lymphoblastic leukemia;
CRLF2; High risk; Pediatric leukemia; Prognostic marker; T acute lymphoblastic leukemia; Oncology
English
59260
59272
13
Palmi, C., Savino, A., Silvestri, D., Bronzini, I., Cario, G., Paganin, M., et al. (2016). CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia. ONCOTARGET, 7(37), 59260-59272 [10.18632/oncotarget.10610].
Palmi, C; Savino, A; Silvestri, D; Bronzini, I; Cario, G; Paganin, M; Buldini, B; Galbiati, M; Muckenthaler, M; Bugarin, C; Mina, P; Nagel, S; Barisone, E; Casale, F; Locatelli, F; Nigro, L; Micalizzi, C; Parasole, R; Pession, A; Putti, M; Santoro, N; Testi, A; Ziino, O; Kulozik, A; Zimmermann, M; Schrappe, M; Villa, A; Gaipa, G; Basso, G; Biondi, A; Valsecchi, M; Stanulla, M; Conter, V; Kronnie, G; Cazzaniga, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/141431
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