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803 results on '"Nigro L"'

1. The KMT2A recombinome of acute leukemias in 2023

Author

Meyer, C., Larghero, P., Almeida Lopes, B., Burmeister, T., Gröger, D., Sutton, R., Venn, N. C., Cazzaniga, G., Corral Abascal, L., Tsaur, G., Fechina, L., Emerenciano, M., Pombo-de-Oliveira, M. S., Lund-Aho, T., Lundán, T., Montonen, M., Juvonen, V., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., Van der Velden, V. H. J., Sonneveld, E., Delabesse, E., de Matos, R. R. C., Silva, M. L. M., Bomken, S., Katsibardi, K., Keernik, M., Grardel, N., Mason, J., Price, R., Kim, J., Eckert, C., Lo Nigro, L., Bueno, C., Menendez, P., zur Stadt, U., Gameiro, P., Sedék, L., Szczepański, T., Bidet, A., Marcu, V., Shichrur, K., Izraeli, S., Madsen, H. O., Schäfer, B. W., Kubetzko, S., Kim, R., Clappier, E., Trautmann, H., Brüggemann, M., Archer, P., Hancock, J., Alten, J., Möricke, A., Stanulla, M., Lentes, J., Bergmann, A. K., Strehl, S., Köhrer, S., Nebral, K., Dworzak, M. N., Haas, O. A., Arfeuille, C., Caye-Eude, A., Cavé, H., and Marschalek, R.

Published
2023
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3. Biomonitoring of human activities recovery following lockdown in a highly touristic Mediterranean Island using Mytilus galloprovincialis

Author

Della Torre, C, Villa, S, Chiarore, A, Cannavacciuolo, A, Rizzi, C, Musco, L, Nigro, L, Munari, M, Della Torre, C, Villa, S, Chiarore, A, Cannavacciuolo, A, Rizzi, C, Musco, L, Nigro, L, and Munari, M

Abstract

Coastal waters face significant anthropogenic stress, particularly from tourism, exacerbating pollution, especially in areas like touristic islands. Ischia, the largest island in the Gulf of Naples and part of the Regno di Nettuno Marine Protected Area, suffers from pollution due to tourism and maritime traffic. During the initial SARS-CoV-2 lockdown from March to June 2020, Ischia was isolated, providing a unique opportunity to study pollutant release and its impact on coastal ecosystems. Adult Mytilus galloprovincialis mussels were transplanted to three sites on the island for active biomonitoring. Accumulation of chemicals in tissues and biomarkers related to metabolism, detoxification, and oxidative stress were measured. Results indicated that pollutants from daily activities entered the sea, affecting filter feeders. Translocated organisms showed modulated metabolic functions and biochemical changes, highlighting coastal vulnerability and calling for conservation efforts.

Published
2024

4. Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia

Author

Palmi, C, Bresolin, S, Junk, S, Fazio, G, Silvestri, D, Zaliova, M, Oikonomou, A, Scharov, K, Stanulla, M, Moericke, A, Zimmermann, M, Schrappe, M, Buldini, B, Bhatia, S, Borkhardt, A, Saitta, C, Galbiati, M, Bardini, M, Lo Nigro, L, Conter, V, Valsecchi, M, Biondi, A, Te Kronnie, G, Cario, G, Cazzaniga, G, Palmi C., Bresolin S., Junk S., Fazio G., Silvestri D., Zaliova M., Oikonomou A., Scharov K., Stanulla M., Moericke A., Zimmermann M., Schrappe M., Buldini B., Bhatia S., Borkhardt A., Saitta C., Galbiati M., Bardini M., Lo Nigro L., Conter V., Valsecchi M. G., Biondi A., Te Kronnie G., Cario G., Cazzaniga G., Palmi, C, Bresolin, S, Junk, S, Fazio, G, Silvestri, D, Zaliova, M, Oikonomou, A, Scharov, K, Stanulla, M, Moericke, A, Zimmermann, M, Schrappe, M, Buldini, B, Bhatia, S, Borkhardt, A, Saitta, C, Galbiati, M, Bardini, M, Lo Nigro, L, Conter, V, Valsecchi, M, Biondi, A, Te Kronnie, G, Cario, G, Cazzaniga, G, Palmi C., Bresolin S., Junk S., Fazio G., Silvestri D., Zaliova M., Oikonomou A., Scharov K., Stanulla M., Moericke A., Zimmermann M., Schrappe M., Buldini B., Bhatia S., Borkhardt A., Saitta C., Galbiati M., Bardini M., Lo Nigro L., Conter V., Valsecchi M. G., Biondi A., Te Kronnie G., Cario G., and Cazzaniga G.

Abstract

Children with Down syndrome have an augmented risk for B-cell acute lymphoblastic leukemia (DS-ALL), which is associated with lower survival than in non-DS-ALL. It is known that cytogenetic abnormalities common in childhood ALL are less frequent in DS-ALL, while other genetic aberrancies (ie, CRLF2 overexpression and IKZF1 deletions) are increased. A possible cause for the lower survival of DS-ALL that we herewith evaluated for the first time was the incidence and prognostic value of the Philadelphia-like (Ph-like) profile and the IKZF1plus pattern. These features have been associated with poor outcome in non-DS ALL and therefore introduced in current therapeutic protocols. Forty-six out of 70 DS-ALL patients treated in Italy from 2000 to 2014 displayed Ph-like signature, mostly characterized by CRLF2 (n = 33) and IKZF1 (n = 16) alterations; only 2 cases were positive for ABL-class or PAX5-fusion genes. Moreover, in an Italian and German joint cohort of 134 DS-ALL patients, we observed 18% patients positive for IKZF1plus feature. Ph-like signature and IKZF1 deletion were associated with poor outcome (cumulative incidence of relapse: 27.7 ± 6.8% versus 13 ± 7%; P = 0.04 and 35.2 ± 8.6% versus 17 ± 3.9%; P = 0.007, respectively), which further worsens when IKZF1 deletion was co-occurring with P2RY8::CRLF2, qualifying for the IKZF1plus definition (13/15 patients had an event of relapse or treatment-related death). Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.

Published
2023

7. Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement

Author

Bomken, S, Enshaei, A, Schwalbe, E, Mikulasova, A, Dai, Y, Zaka, M, Fung, K, Bashton, M, Lim, H, Jones, L, Karataraki, N, Winterman, E, Ashby, C, Attarbaschi, A, Bertrand, Y, Bradtke, J, Buldini, B, Burke, G, Cazzaniga, G, Gohring, G, De Groot-Kruseman, H, Haferlach, C, Nigro, L, Parihar, M, Plesa, A, Seaford, E, Sonneveld, E, Strehl, S, Van der Velden, V, Rand, V, Hunger, S, Harrison, C, Bacon, C, Van Delft, F, Loh, M, Moppett, J, Vormoor, J, Walker, B, Moorman, A, Russell, L, Bomken, Simon, Enshaei, Amir, Schwalbe, Edward C, Mikulasova, Aneta, Dai, Yunfeng, Zaka, Masood, Fung, Kent Tm, Bashton, Matthew, Lim, Huezin, Jones, Lisa, Karataraki, Nefeli, Winterman, Emily, Ashby, Cody, Attarbaschi, Andishe, Bertrand, Yves, Bradtke, Jutta, Buldini, Barbara, Burke, G. A. Amos, Cazzaniga, Giovanni, Gohring, Gudrun, De Groot-Kruseman, Hesta A, Haferlach, Claudia, Nigro, Luca Lo, Parihar, Mayur, Plesa, Adriana, Seaford, Emma, Sonneveld, Edwin, Strehl, Sabine, Van der Velden, Vincent Hj, Rand, Vikki, Hunger, Stephen P, Harrison, Christine J, Bacon, Chris M, Van Delft, Frederik W, Loh, Mignon L, Moppett, John, Vormoor, Josef, Walker, Brian A, Moorman, Anthony V, Russell, Lisa J, Bomken, S, Enshaei, A, Schwalbe, E, Mikulasova, A, Dai, Y, Zaka, M, Fung, K, Bashton, M, Lim, H, Jones, L, Karataraki, N, Winterman, E, Ashby, C, Attarbaschi, A, Bertrand, Y, Bradtke, J, Buldini, B, Burke, G, Cazzaniga, G, Gohring, G, De Groot-Kruseman, H, Haferlach, C, Nigro, L, Parihar, M, Plesa, A, Seaford, E, Sonneveld, E, Strehl, S, Van der Velden, V, Rand, V, Hunger, S, Harrison, C, Bacon, C, Van Delft, F, Loh, M, Moppett, J, Vormoor, J, Walker, B, Moorman, A, Russell, L, Bomken, Simon, Enshaei, Amir, Schwalbe, Edward C, Mikulasova, Aneta, Dai, Yunfeng, Zaka, Masood, Fung, Kent Tm, Bashton, Matthew, Lim, Huezin, Jones, Lisa, Karataraki, Nefeli, Winterman, Emily, Ashby, Cody, Attarbaschi, Andishe, Bertrand, Yves, Bradtke, Jutta, Buldini, Barbara, Burke, G. A. Amos, Cazzaniga, Giovanni, Gohring, Gudrun, De Groot-Kruseman, Hesta A, Haferlach, Claudia, Nigro, Luca Lo, Parihar, Mayur, Plesa, Adriana, Seaford, Emma, Sonneveld, Edwin, Strehl, Sabine, Van der Velden, Vincent Hj, Rand, Vikki, Hunger, Stephen P, Harrison, Christine J, Bacon, Chris M, Van Delft, Frederik W, Loh, Mignon L, Moppett, John, Vormoor, Josef, Walker, Brian A, Moorman, Anthony V, and Russell, Lisa J

Abstract

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either established BCP-ALL-specific abnormalities (high hyperdiploidy, n=3; KMT2A-rearrangement, n=6; iAMP21, n=1; BCR-ABL1, n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J-rearranged cases, clearly distinct from Burkitt leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.

Published
2023

8. Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25-year Italian experience

Author

Testi, A, Mohamed, S, Diverio, D, Piciocchi, A, Menna, G, Rizzari, C, Timeus, F, Micalizzi, C, Lo Nigro, L, Santoro, N, Masetti, R, Micheletti, M, Ziino, O, Onofrillo, D, Ladogana, S, Putti, C, Pierani, P, Arena, V, Zecca, M, Foa, R, Locatelli, F, Testi A. M., Mohamed S., Diverio D., Piciocchi A., Menna G., Rizzari C., Timeus F., Micalizzi C., Lo Nigro L., Santoro N., Masetti R., Micheletti M. V., Ziino O., Onofrillo D., Ladogana S., Putti C., Pierani P., Arena V., Zecca M., Foa R., Locatelli F., Testi, A, Mohamed, S, Diverio, D, Piciocchi, A, Menna, G, Rizzari, C, Timeus, F, Micalizzi, C, Lo Nigro, L, Santoro, N, Masetti, R, Micheletti, M, Ziino, O, Onofrillo, D, Ladogana, S, Putti, C, Pierani, P, Arena, V, Zecca, M, Foa, R, Locatelli, F, Testi A. M., Mohamed S., Diverio D., Piciocchi A., Menna G., Rizzari C., Timeus F., Micalizzi C., Lo Nigro L., Santoro N., Masetti R., Micheletti M. V., Ziino O., Onofrillo D., Ladogana S., Putti C., Pierani P., Arena V., Zecca M., Foa R., and Locatelli F.

Published
2021

9. CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript

Author

Zangrando, A, Cavagnero, F, Scarparo, P, Varotto, E, Francescato, S, Tregnago, C, Cuccurullo, R, Fagioli, F, Nigro, L, Masetti, R, Putti, M, Rizzari, C, Santoro, N, Pession, A, Pigazzi, M, Locatelli, F, Basso, G, Buldini, B, Zangrando A., Cavagnero F., Scarparo P., Varotto E., Francescato S., Tregnago C., Cuccurullo R., Fagioli F., Nigro L. L., Masetti R., Putti M. C., Rizzari C., Santoro N., Pession A., Pigazzi M., Locatelli F., Basso G., Buldini B., Zangrando, A, Cavagnero, F, Scarparo, P, Varotto, E, Francescato, S, Tregnago, C, Cuccurullo, R, Fagioli, F, Nigro, L, Masetti, R, Putti, M, Rizzari, C, Santoro, N, Pession, A, Pigazzi, M, Locatelli, F, Basso, G, Buldini, B, Zangrando A., Cavagnero F., Scarparo P., Varotto E., Francescato S., Tregnago C., Cuccurullo R., Fagioli F., Nigro L. L., Masetti R., Putti M. C., Rizzari C., Santoro N., Pession A., Pigazzi M., Locatelli F., Basso G., and Buldini B.

Abstract

The presence of CBFA2T3-GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML-CBFA2T3-GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3-GLIS2-AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3-GLIS2-AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA-DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak-to-negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA-DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

Published
2021

10. Single-cell profiling of pediatric T-cell acute lymphoblastic leukemia: Impact of PTEN exon 7 mutation on PI3K/Akt and JAK–STAT signaling pathways

Author

Bonaccorso, P, Bugarin, C, Buracchi, C, Fazio, G, Biondi, A, Lo Nigro, L, Gaipa, G, Bonaccorso P., Bugarin C., Buracchi C., Fazio G., Biondi A., Lo Nigro L., Gaipa G., Bonaccorso, P, Bugarin, C, Buracchi, C, Fazio, G, Biondi, A, Lo Nigro, L, Gaipa, G, Bonaccorso P., Bugarin C., Buracchi C., Fazio G., Biondi A., Lo Nigro L., and Gaipa G.

Abstract

Background: The PI3K/Akt/mTOR (PI3K) signaling pathway has a crucial role in T-cell acute lymphoblastic leukemias (T-ALLs). Although loss-of-function of phosphatase and tensin homolog (PTEN) is a common event in pediatric T-ALLs, the exact role of this tumor suppressor in T-ALL development has yet to be defined. Methods: Here, we report an optimized cytometric method for accurate proteomic profiling of T-ALL leukemic blasts at single-cell level. We determined the expression of PI3K and JAK–STAT signaling components in both primary and immortalized T-ALL cells as well as in normal T cells. Results: We observed that PTEN exon 7 mutated T-ALL cells retain a distinct PI3K activation; in particular, these cells show higher pAkt levels and a lower pS6 expression. Interestingly, we demonstrated for the first time that PTEN exon 7 mutated T-ALL are nonresponsive to IL7 in vitro as assessed by lack of pSTAT5 activation, although they do express IL7R. Conclusions: Phosphoflow analysis represents a fast, reliable, and accurate method to study the signaling profile of T-ALL. PTEN exon 7 mutated T-ALL cells are nonresponsive to IL7 in vitro suggesting that they may activate other mechanisms to support their viability and proliferation such as a higher constitutive PI3K/Akt signaling. Further investigations are necessary to elucidate the significance of this peculiar signaling behavior. Our observations should be taken into account in future studies aiming at molecular targeting of PI3K and/or JAK/STAT pathways for pharmacological intervention in T-ALL.

Published
2020

11. Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial

Author

Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., Schrappe M., Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., and Schrappe M.

Published
2020

12. Molecular characterisation and clinical outcome of B-cell precursor acute lymphoblastic leukaemia with IG-MYC rearrangement

Author

Bomken, S, Enshaei, A, Schwalbe, E, Mikulasova, A, Dai, Y, Zaka, M, Fung, K, Bashton, M, Lim, H, Jones, L, Karataraki, N, Winterman, E, Ashby, C, Attarbaschi, A, Bertrand, Y, Bradtke, J, Buldini, B, Burke, G, Cazzaniga, G, Gohring, G, De Groot-Kruseman, H, Haferlach, C, Nigro, L, Parihar, M, Plesa, A, Seaford, E, Sonneveld, E, Strehl, S, Van der Velden, V, Rand, V, Hunger, S, Harrison, C, Bacon, C, Van Delft, F, Loh, M, Moppett, J, Vormoor, J, Walker, B, Moorman, A, Russell, L, Bomken, Simon, Enshaei, Amir, Schwalbe, Edward C, Mikulasova, Aneta, Dai, Yunfeng, Zaka, Masood, Fung, Kent Tm, Bashton, Matthew, Lim, Huezin, Jones, Lisa, Karataraki, Nefeli, Winterman, Emily, Ashby, Cody, Attarbaschi, Andishe, Bertrand, Yves, Bradtke, Jutta, Buldini, Barbara, Burke, G. A. Amos, Cazzaniga, Giovanni, Gohring, Gudrun, De Groot-Kruseman, Hesta A, Haferlach, Claudia, Nigro, Luca Lo, Parihar, Mayur, Plesa, Adriana, Seaford, Emma, Sonneveld, Edwin, Strehl, Sabine, Van der Velden, Vincent Hj, Rand, Vikki, Hunger, Stephen P, Harrison, Christine J, Bacon, Chris M, Van Delft, Frederik W, Loh, Mignon L, Moppett, John, Vormoor, Josef, Walker, Brian A, Moorman, Anthony V, Russell, Lisa J, Bomken, S, Enshaei, A, Schwalbe, E, Mikulasova, A, Dai, Y, Zaka, M, Fung, K, Bashton, M, Lim, H, Jones, L, Karataraki, N, Winterman, E, Ashby, C, Attarbaschi, A, Bertrand, Y, Bradtke, J, Buldini, B, Burke, G, Cazzaniga, G, Gohring, G, De Groot-Kruseman, H, Haferlach, C, Nigro, L, Parihar, M, Plesa, A, Seaford, E, Sonneveld, E, Strehl, S, Van der Velden, V, Rand, V, Hunger, S, Harrison, C, Bacon, C, Van Delft, F, Loh, M, Moppett, J, Vormoor, J, Walker, B, Moorman, A, Russell, L, Bomken, Simon, Enshaei, Amir, Schwalbe, Edward C, Mikulasova, Aneta, Dai, Yunfeng, Zaka, Masood, Fung, Kent Tm, Bashton, Matthew, Lim, Huezin, Jones, Lisa, Karataraki, Nefeli, Winterman, Emily, Ashby, Cody, Attarbaschi, Andishe, Bertrand, Yves, Bradtke, Jutta, Buldini, Barbara, Burke, G. A. Amos, Cazzaniga, Giovanni, Gohring, Gudrun, De Groot-Kruseman, Hesta A, Haferlach, Claudia, Nigro, Luca Lo, Parihar, Mayur, Plesa, Adriana, Seaford, Emma, Sonneveld, Edwin, Strehl, Sabine, Van der Velden, Vincent Hj, Rand, Vikki, Hunger, Stephen P, Harrison, Christine J, Bacon, Chris M, Van Delft, Frederik W, Loh, Mignon L, Moppett, John, Vormoor, Josef, Walker, Brian A, Moorman, Anthony V, and Russell, Lisa J

Abstract

Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) carries an immunoglobulin-MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukaemia and use of unproven individualised treatment schedules. Here we contrast the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered on a national BCP-ALL clinical trial/registry. Where present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analysis. Outcome was analysed to define 3-year event free survival (EFS) and overall survival (OS). IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either: established BCP-ALL specific abnormalities (high hyperdiploidy n=3, KMT2A-rearrangement n=6, iAMP21 n=1, BCR-ABL n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J rearranged cases, clearly distinct from Burkitt leukaemia/lymphoma. Children with IG-MYC-r within that subgroup had 3-year EFS of 47% and OS of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this patient group must be allowed access to contemporary, minimal residual disease adapted, prospective clinical trial protocols.

Published
2022

13. FLT3-ITD in Children with Early T-cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD)

Author

Locatelli, F, Lo Nigro, L, Andriano, N, Buldini, B, Silvestri, D, Villa, T, Parasole, R, Barisone, E, Testi, A, Biondi, A, Valsecchi, M, Rizzari, C, Conter, V, Basso, G, Cazzaniga, G, Locatelli, Franco, Lo Nigro, Luca, Andriano, Nellina, Buldini, Barbara, Silvestri, Daniela, Villa, Tiziana, Parasole, Rosanna, Barisone, Elena, Testi, Anna Maria, Biondi, Andrea, Valsecchi, Maria Grazia, Rizzari, Carmelo, Conter, Valentino, Basso, Giuseppe, Cazzaniga, Giovanni, Locatelli, F, Lo Nigro, L, Andriano, N, Buldini, B, Silvestri, D, Villa, T, Parasole, R, Barisone, E, Testi, A, Biondi, A, Valsecchi, M, Rizzari, C, Conter, V, Basso, G, Cazzaniga, G, Locatelli, Franco, Lo Nigro, Luca, Andriano, Nellina, Buldini, Barbara, Silvestri, Daniela, Villa, Tiziana, Parasole, Rosanna, Barisone, Elena, Testi, Anna Maria, Biondi, Andrea, Valsecchi, Maria Grazia, Rizzari, Carmelo, Conter, Valentino, Basso, Giuseppe, and Cazzaniga, Giovanni

Abstract

Early T‐cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3‐ ITD was identified in 35% cases of adult ETP‐ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T‐cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T‐ALL enrolled in Italy into AIEOP‐BFM‐ ALL2000, AIEOP‐ALLR2006, and AIEOP‐BFM‐ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3‐ITD. A total of 10 out of 77 (13%) ETP cases were FLT3‐ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3‐ITD MRD monitoring was performed using real‐time PCR in all FLT3‐ITD positive ETP cases. A comparison between IG/TR and FLT3‐ITD resulted in comparable findings. Our study demonstrated that the FLT3‐ITD prevalence in children was lower (13%) than that reported in adult ETP‐ALL. FLT3‐ITD can be used as a marker for sensitive molecular MRD monitoring in ETP‐ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia.

Published
2022

14. FLT3‐ITD in Children with Early T‐cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD)

Author

Lo Nigro, L., Andriano, N., Buldini, B., Silvestri, D., Villa, T., Locatelli, Franco, Parasole, R., Barisone, E., Testi, A. M., Biondi, A., Valsecchi, M. G., Rizzari, C., Conter, V., Basso, G., Cazzaniga, G., Locatelli F. (ORCID:0000-0002-7976-3654), Lo Nigro, L., Andriano, N., Buldini, B., Silvestri, D., Villa, T., Locatelli, Franco, Parasole, R., Barisone, E., Testi, A. M., Biondi, A., Valsecchi, M. G., Rizzari, C., Conter, V., Basso, G., Cazzaniga, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Early T‐cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3‐ ITD was identified in 35% cases of adult ETP‐ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T‐cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T‐ALL enrolled in Italy into AIEOP‐BFM‐ ALL2000, AIEOP‐ALLR2006, and AIEOP‐BFM‐ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3‐ITD. A total of 10 out of 77 (13%) ETP cases were FLT3‐ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3‐ITD MRD monitoring was performed using real‐time PCR in all FLT3‐ITD positive ETP cases. A comparison between IG/TR and FLT3‐ITD resulted in comparable findings. Our study demonstrated that the FLT3‐ITD prevalence in children was lower (13%) than that reported in adult ETP‐ALL. FLT3‐ITD can be used as a marker for sensitive molecular MRD monitoring in ETP‐ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia.

Published
2022

15. PAX5 fusion genes are frequent in poor risk childhood acute lymphoblastic leukaemia and can be targeted with BIBF1120

Author

Fazio, G., Bresolin, S., Silvestri, D., Quadri, M., Saitta, C., Vendramini, E., Buldini, B., Palmi, C., Bardini, M., Grioni, A., Rigamonti, S., Galbiati, M., Mecca, S., Savino, A. M., Peloso, A., Tu, J. -W., Bhatia, S., Borkhardt, A., Micalizzi, C., Lo Nigro, L., Locatelli, Franco, Conter, V., Rizzari, C., Valsecchi, M. G., te Kronnie, G., Biondi, A., Cazzaniga, G., Locatelli F. (ORCID:0000-0002-7976-3654), Fazio, G., Bresolin, S., Silvestri, D., Quadri, M., Saitta, C., Vendramini, E., Buldini, B., Palmi, C., Bardini, M., Grioni, A., Rigamonti, S., Galbiati, M., Mecca, S., Savino, A. M., Peloso, A., Tu, J. -W., Bhatia, S., Borkhardt, A., Micalizzi, C., Lo Nigro, L., Locatelli, Franco, Conter, V., Rizzari, C., Valsecchi, M. G., te Kronnie, G., Biondi, A., Cazzaniga, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: Despite intensive risk-based treatment protocols, 15% of paediatric patients with B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL) experience relapse. There is urgent need of novel strategies to target poor prognosis subgroups, like PAX5 translocated. Methods: We considered 289 childhood BCP-ALL cases consecutively enrolled in Italy in the AIEOP-BFM ALL2000/R2006 protocols and we performed extensive molecular profiling, integrating gene expression, copy number analyses and fusion genes discovery by target-capture NGS. We developed preclinical strategies to target PAX5 fusion genes. Findings: We identified 135 cases without recurrent genetic rearrangements. Among them, 59 patients (43·7%) had a Ph-like signature; the remaining cases were identified as ERG-related (26%), High-Hyperdiploid-like (17%), ETV6::RUNX1-like (8·9%), MEF2D-rearranged (2·2%) or KMT2A-like (1·5%). A poor prognosis was associated with the Ph-like signature, independently from other high-risk features. Interestingly, PAX5 was altered in 54·4% of Ph-like compared to 16·2% of non-Ph-like cases, with 7 patients carrying PAX5 fusions (PAX5t), involving either novel (ALDH18A1, IKZF1, CDH13) or known (FBRSL1, AUTS2, DACH2) partner genes. PAX5t cases have a specific driver activity signature, extending to multiple pathways including LCK hyperactivation. Among FDA-approved drugs and inhibitors, we selected Dasatinib, Bosutinib and Foretinib, in addition to Nintedanib, known to be LCK ligands. We demonstrated the efficacy of the LCK-inhibitor BIBF1120/Nintedanib, as single agent or in combination with conventional chemotherapy, both ex vivo and in patient-derived xenograft model, showing a synergistic effect with dexamethasone. Interpretation: This study provides new insights in high-risk Ph-like leukaemia and identifies a potential therapy for targeting PAX5-fusion poor risk group. Funding: Ricerca Finalizzata-Giovani Ricercatori (Italian Ministry of Health), AIRC, Transcall, Fondazion

Published
2022

16. Antibiotic prophylaxis and management of infections in pediatric hematopoietic stem cell transplantation: a survey from the Stem Cell Transplant and the Infectious Disease Working Groups of the AIEOP network

Author

Zama, D., Masetti, R., Baccelli, F., Leardini, D., Muratore, E., Abram, N., Vendemini, F., Biffi, A., Perruccio, K., D'Amico, M. R., Faraci, M., Tintori, V., Spirito, A., Lo Nigro, L., Locatelli, Franco, Luksch, R., Saglio, F., Santoro, N., Soncini, E., Zecca, M., Ziino, O., Prete, A., Pagliara, D., Cesaro, S., Locatelli F. (ORCID:0000-0002-7976-3654), Zama, D., Masetti, R., Baccelli, F., Leardini, D., Muratore, E., Abram, N., Vendemini, F., Biffi, A., Perruccio, K., D'Amico, M. R., Faraci, M., Tintori, V., Spirito, A., Lo Nigro, L., Locatelli, Franco, Luksch, R., Saglio, F., Santoro, N., Soncini, E., Zecca, M., Ziino, O., Prete, A., Pagliara, D., Cesaro, S., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2022

17. PAX5 fusion genes are frequent in poor risk childhood acute lymphoblastic leukaemia and can be targeted with BIBF1120

Author

Fazio, G, Bresolin, S, Silvestri, D, Quadri, M, Saitta, C, Vendramini, E, Buldini, B, Palmi, C, Bardini, M, Grioni, A, Rigamonti, S, Galbiati, M, Mecca, S, Savino, A, Peloso, A, Tu, J, Bhatia, S, Borkhardt, A, Micalizzi, C, Lo Nigro, L, Locatelli, F, Conter, V, Rizzari, C, Valsecchi, M, Te Kronnie, G, Biondi, A, Cazzaniga, G, Fazio, Grazia, Bresolin, Silvia, Silvestri, Daniela, Quadri, Manuel, Saitta, Claudia, Vendramini, Elena, Buldini, Barbara, Palmi, Chiara, Bardini, Michela, Grioni, Andrea, Rigamonti, Silvia, Galbiati, Marta, Mecca, Stefano, Savino, Angela Maria, Peloso, Alberto, Tu, Jia-Wey, Bhatia, Sanil, Borkhardt, Arndt, Micalizzi, Concetta, Lo Nigro, Luca, Locatelli, Franco, Conter, Valentino, Rizzari, Carmelo, Valsecchi, Maria Grazia, Te Kronnie, Geertruij, Biondi, Andrea, Cazzaniga, Giovanni, Fazio, G, Bresolin, S, Silvestri, D, Quadri, M, Saitta, C, Vendramini, E, Buldini, B, Palmi, C, Bardini, M, Grioni, A, Rigamonti, S, Galbiati, M, Mecca, S, Savino, A, Peloso, A, Tu, J, Bhatia, S, Borkhardt, A, Micalizzi, C, Lo Nigro, L, Locatelli, F, Conter, V, Rizzari, C, Valsecchi, M, Te Kronnie, G, Biondi, A, Cazzaniga, G, Fazio, Grazia, Bresolin, Silvia, Silvestri, Daniela, Quadri, Manuel, Saitta, Claudia, Vendramini, Elena, Buldini, Barbara, Palmi, Chiara, Bardini, Michela, Grioni, Andrea, Rigamonti, Silvia, Galbiati, Marta, Mecca, Stefano, Savino, Angela Maria, Peloso, Alberto, Tu, Jia-Wey, Bhatia, Sanil, Borkhardt, Arndt, Micalizzi, Concetta, Lo Nigro, Luca, Locatelli, Franco, Conter, Valentino, Rizzari, Carmelo, Valsecchi, Maria Grazia, Te Kronnie, Geertruij, Biondi, Andrea, and Cazzaniga, Giovanni

Abstract

Background: Despite intensive risk-based treatment protocols, 15% of paediatric patients with B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL) experience relapse. There is urgent need of novel strategies to target poor prognosis subgroups, like PAX5 translocated. Methods: We considered 289 childhood BCP-ALL cases consecutively enrolled in Italy in the AIEOP-BFM ALL2000/R2006 protocols and we performed extensive molecular profiling, integrating gene expression, copy number analyses and fusion genes discovery by target-capture NGS. We developed preclinical strategies to target PAX5 fusion genes. Findings: We identified 135 cases without recurrent genetic rearrangements. Among them, 59 patients (43·7%) had a Ph-like signature; the remaining cases were identified as ERG-related (26%), High-Hyperdiploid-like (17%), ETV6::RUNX1-like (8·9%), MEF2D-rearranged (2·2%) or KMT2A-like (1·5%). A poor prognosis was associated with the Ph-like signature, independently from other high-risk features. Interestingly, PAX5 was altered in 54·4% of Ph-like compared to 16·2% of non-Ph-like cases, with 7 patients carrying PAX5 fusions (PAX5t), involving either novel (ALDH18A1, IKZF1, CDH13) or known (FBRSL1, AUTS2, DACH2) partner genes. PAX5t cases have a specific driver activity signature, extending to multiple pathways including LCK hyperactivation. Among FDA-approved drugs and inhibitors, we selected Dasatinib, Bosutinib and Foretinib, in addition to Nintedanib, known to be LCK ligands. We demonstrated the efficacy of the LCK-inhibitor BIBF1120/Nintedanib, as single agent or in combination with conventional chemotherapy, both ex vivo and in patient-derived xenograft model, showing a synergistic effect with dexamethasone. Interpretation: This study provides new insights in high-risk Ph-like leukaemia and identifies a potential therapy for targeting PAX5-fusion poor risk group. Funding: Ricerca Finalizzata-Giovani Ricercatori (Italian Ministry of Health), AIRC, Transcall, Fondazion

Published
2022

19. CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript

Author

Zangrando, A., Cavagnero, F., Scarparo, P., Varotto, E., Francescato, S., Tregnago, C., Cuccurullo, R., Fagioli, F., Nigro, L. L., Masetti, R., Putti, M. C., Rizzari, C., Santoro, N., Pession, A., Pigazzi, M., Locatelli, F., Basso, G., Buldini, B., Zangrando, A, Cavagnero, F, Scarparo, P, Varotto, E, Francescato, S, Tregnago, C, Cuccurullo, R, Fagioli, F, Nigro, L, Masetti, R, Putti, M, Rizzari, C, Santoro, N, Pession, A, Pigazzi, M, Locatelli, F, Basso, G, Buldini, B, Zangrando A., Cavagnero F., Scarparo P., Varotto E., Francescato S., Tregnago C., Cuccurullo R., Fagioli F., Nigro L.L., Masetti R., Putti M.C., Rizzari C., Santoro N., Pession A., Pigazzi M., Locatelli F., Basso G., and Buldini B.

Subjects
Oncogene Proteins, Fusion, Brief Report, HLA-DR Antigens, acute myeloid leukemia, Repressor Proteins, CBFA2T3‐GLIS2, Leukemia, Myeloid, Acute, computational analysi, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, immunophenotyping, computational analysis, hemic and lymphatic diseases, Humans, CBFA2T3-GLIS2, Child, Transcriptome
Abstract

The presence of CBFA2T3‐GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML‐CBFA2T3‐GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3‐GLIS2‐AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3‐GLIS2‐AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA‐DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak‐to‐negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA‐DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

Published
2021

21. Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25-year Italian experience

Author

Testi, A. M., Mohamed, S., Diverio, D., Piciocchi, A., Menna, G., Rizzari, C., Timeus, F., Micalizzi, C., Lo Nigro, L., Santoro, N., Masetti, R., Micheletti, M. V., Ziino, O., Onofrillo, D., Ladogana, S., Putti, C., Pierani, P., Arena, V., Zecca, M., Foa, R., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Testi, A. M., Mohamed, S., Diverio, D., Piciocchi, A., Menna, G., Rizzari, C., Timeus, F., Micalizzi, C., Lo Nigro, L., Santoro, N., Masetti, R., Micheletti, M. V., Ziino, O., Onofrillo, D., Ladogana, S., Putti, C., Pierani, P., Arena, V., Zecca, M., Foa, R., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

no abstract

Published
2021

22. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Author

Stutterheim, J., van der Sluis, I. M., de Lorenzo, P., Alten, J., Ancliffe, P., Attarbaschi, A., Brethon, B., Biondi, A., Campbell, M., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Li, C. K., Lo Nigro, L., Locatelli, Franco, Marschalek, R., Meyer, C., Schrappe, M., Stary, J., Vora, A., Zuna, J., van der Velden, V. H. J., Szczepanski, T., Valsecchi, M. G., Pieters, R., Locatelli F. (ORCID:0000-0002-7976-3654), Stutterheim, J., van der Sluis, I. M., de Lorenzo, P., Alten, J., Ancliffe, P., Attarbaschi, A., Brethon, B., Biondi, A., Campbell, M., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Li, C. K., Lo Nigro, L., Locatelli, Franco, Marschalek, R., Meyer, C., Schrappe, M., Stary, J., Vora, A., Zuna, J., van der Velden, V. H. J., Szczepanski, T., Valsecchi, M. G., Pieters, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may bene

Published
2021

23. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Author

Stutterheim, J, van der Sluis, I, de Lorenzo, P, Alten, J, Ancliffe, P, Attarbaschi, A, Brethon, B, Biondi, A, Campbell, M, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Li, C, Lo Nigro, L, Locatelli, F, Marschalek, R, Meyer, C, Schrappe, M, Stary, J, Vora, A, Zuna, J, van der Velden, V, Szczepanski, T, Valsecchi, M, Pieters, R, Stutterheim, Janine, van der Sluis, Inge M, de Lorenzo, Paola, Alten, Julia, Ancliffe, Philip, Attarbaschi, Andishe, Brethon, Benoit, Biondi, Andrea, Campbell, Myriam, Cazzaniga, Giovanni, Escherich, Gabriele, Ferster, Alina, Kotecha, Rishi S, Lausen, Birgitte, Li, Chi Kong, Lo Nigro, Luca, Locatelli, Franco, Marschalek, Rolf, Meyer, Claus, Schrappe, Martin, Stary, Jan, Vora, Ajay, Zuna, Jan, van der Velden, Vincent H J, Szczepanski, Tomasz, Valsecchi, Maria Grazia, Pieters, Rob, Stutterheim, J, van der Sluis, I, de Lorenzo, P, Alten, J, Ancliffe, P, Attarbaschi, A, Brethon, B, Biondi, A, Campbell, M, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Li, C, Lo Nigro, L, Locatelli, F, Marschalek, R, Meyer, C, Schrappe, M, Stary, J, Vora, A, Zuna, J, van der Velden, V, Szczepanski, T, Valsecchi, M, Pieters, R, Stutterheim, Janine, van der Sluis, Inge M, de Lorenzo, Paola, Alten, Julia, Ancliffe, Philip, Attarbaschi, Andishe, Brethon, Benoit, Biondi, Andrea, Campbell, Myriam, Cazzaniga, Giovanni, Escherich, Gabriele, Ferster, Alina, Kotecha, Rishi S, Lausen, Birgitte, Li, Chi Kong, Lo Nigro, Luca, Locatelli, Franco, Marschalek, Rolf, Meyer, Claus, Schrappe, Martin, Stary, Jan, Vora, Ajay, Zuna, Jan, van der Velden, Vincent H J, Szczepanski, Tomasz, Valsecchi, Maria Grazia, and Pieters, Rob

Abstract

Purpose: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). Materials and methods: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). Results: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). Conclusion: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may bene

Published
2021

26. New insights to the MLL recombinome of acute leukemias

Author

Meyer, C, Kowarz, E, Hofmann, J, Renneville, A, Zuna, J, Trka, J, Ben Abdelali, R, Macintyre, E, De Braekeleer, E, De Braekeleer, M, Delabesse, E, de Oliveira, M P, Cavé, H, Clappier, E, van Dongen, J J M, Balgobind, B V, van den Heuvel-Eibrink, M M, Beverloo, H B, Panzer-Grümayer, R, Teigler-Schlegel, A, Harbott, J, Kjeldsen, E, Schnittger, S, Koehl, U, Gruhn, B, Heidenreich, O, Chan, L C, Yip, S F, Krzywinski, M, Eckert, C, Möricke, A, Schrappe, M, Alonso, C N, Schäfer, B W, Krauter, J, Lee, D A, zur Stadt, U, Te Kronnie, G, Sutton, R, Izraeli, S, Trakhtenbrot, L, Lo Nigro, L, Tsaur, G, Fechina, L, Szczepanski, T, Strehl, S, Ilencikova, D, Molkentin, M, Burmeister, T, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2009
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29. The KMT2Arecombinome of acute leukemias in 2023

Author

Meyer, C., Larghero, P., Almeida Lopes, B., Burmeister, T., Gröger, D., Sutton, R., Venn, N. C., Cazzaniga, G., Corral Abascal, L., Tsaur, G., Fechina, L., Emerenciano, M., Pombo-de-Oliveira, M. S., Lund-Aho, T., Lundán, T., Montonen, M., Juvonen, V., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., Van der Velden, V. H. J., Sonneveld, E., Delabesse, E., de Matos, R. R. C., Silva, M. L. M., Bomken, S., Katsibardi, K., Keernik, M., Grardel, N., Mason, J., Price, R., Kim, J., Eckert, C., Lo Nigro, L., Bueno, C., Menendez, P., zur Stadt, U., Gameiro, P., Sedék, L., Szczepański, T., Bidet, A., Marcu, V., Shichrur, K., Izraeli, S., Madsen, H. O., Schäfer, B. W., Kubetzko, S., Kim, R., Clappier, E., Trautmann, H., Brüggemann, M., Archer, P., Hancock, J., Alten, J., Möricke, A., Stanulla, M., Lentes, J., Bergmann, A. K., Strehl, S., Köhrer, S., Nebral, K., Dworzak, M. N., Haas, O. A., Arfeuille, C., Caye-Eude, A., Cavé, H., and Marschalek, R.

Abstract

Chromosomal rearrangements of the human KMT2A/MLLgene are associated with de novoas well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2Agene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2Agene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2Adeletion, and one ETV6::RUNX1patient had an KMT2Ainsertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2Arecombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Published
2023
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30. Single-cell profiling of pediatric T-cell acute lymphoblastic leukemia: Impact of PTEN exon 7 mutation on PI3K/Akt and JAK-STAT signaling pathways

Author

Bonaccorso P., Bugarin C., Buracchi C., Fazio G., Biondi A., Lo Nigro L., Gaipa G., Bonaccorso, P, Bugarin, C, Buracchi, C, Fazio, G, Biondi, A, Lo Nigro, L, and Gaipa, G

Subjects
Proteomics, PTEN, Interleukin-7, T-Lymphocytes, phoshoflow, PTEN Phosphohydrolase, acute lymphoblastic leukemia, Exons, interleukin 7, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Gene Expression Regulation, Neoplastic, Interleukin-7 Receptor alpha Subunit, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Mutation, STAT5 Transcription Factor, cell signaling, Humans, Single-Cell Analysis, Child, childhood, Janus Kinases, Signal Transduction
Abstract

Background: The PI3K/Akt/mTOR (PI3K) signaling pathway has a crucial role in T-cell acute lymphoblastic leukemias (T-ALLs). Although loss-of-function of phosphatase and tensin homolog (PTEN) is a common event in pediatric T-ALLs, the exact role of this tumor suppressor in T-ALL development has yet to be defined. Methods: Here, we report an optimized cytometric method for accurate proteomic profiling of T-ALL leukemic blasts at single-cell level. We determined the expression of PI3K and JAK–STAT signaling components in both primary and immortalized T-ALL cells as well as in normal T cells. Results: We observed that PTEN exon 7 mutated T-ALL cells retain a distinct PI3K activation; in particular, these cells show higher pAkt levels and a lower pS6 expression. Interestingly, we demonstrated for the first time that PTEN exon 7 mutated T-ALL are nonresponsive to IL7 in vitro as assessed by lack of pSTAT5 activation, although they do express IL7R. Conclusions: Phosphoflow analysis represents a fast, reliable, and accurate method to study the signaling profile of T-ALL. PTEN exon 7 mutated T-ALL cells are nonresponsive to IL7 in vitro suggesting that they may activate other mechanisms to support their viability and proliferation such as a higher constitutive PI3K/Akt signaling. Further investigations are necessary to elucidate the significance of this peculiar signaling behavior. Our observations should be taken into account in future studies aiming at molecular targeting of PI3K and/or JAK/STAT pathways for pharmacological intervention in T-ALL.

Published
2019

31. Correspondence: Osteonecrosis in childhood acute lymphoblastic leukemia: a retrospective cohort study of the Italian Association of Pediatric Haemato-Oncology (AIEOP)

Author

Parasole, R, Valsecchi, M, Silvestri, D, Locatelli, F, Barisone, E, Petruzziello, F, Putti, M, Micalizzi, C, Colombini, A, Mura, R, Mina, T, Testi, A, Notarangelo, L, Santoro, N, Casini, T, Consarino, C, Nigro, L, Ziino, O, Giagnuolo, G, Rizzari, C, Conter, V, Parasole R., Valsecchi M. G., Silvestri D., Locatelli F., Barisone E., Petruzziello F., Putti M. C., Micalizzi C., Colombini A., Mura R., Mina T., Testi A. M., Notarangelo L. D., Santoro N., Casini T., Consarino C., Nigro L. L., Ziino O., Giagnuolo G., Rizzari C., Conter V., Parasole, R, Valsecchi, M, Silvestri, D, Locatelli, F, Barisone, E, Petruzziello, F, Putti, M, Micalizzi, C, Colombini, A, Mura, R, Mina, T, Testi, A, Notarangelo, L, Santoro, N, Casini, T, Consarino, C, Nigro, L, Ziino, O, Giagnuolo, G, Rizzari, C, Conter, V, Parasole R., Valsecchi M. G., Silvestri D., Locatelli F., Barisone E., Petruzziello F., Putti M. C., Micalizzi C., Colombini A., Mura R., Mina T., Testi A. M., Notarangelo L. D., Santoro N., Casini T., Consarino C., Nigro L. L., Ziino O., Giagnuolo G., Rizzari C., and Conter V.

Published
2018

33. A Novel Procedure for Chronic Sagittal Band Rupture, Permitting Immediate Active Motion and Hand Use During Recovery

Author

Merritt, W and Nigro, L

Subjects
ddc: 610, tendon grafts, relative motion extension orthosis, sagittal band repair, 610 Medical sciences, Medicine, sagittal band rupture, relative motion extension splint
Abstract

Objectives/Interrogation: Chronic sagittal band ruptures have characteristically been treated by surgical techniques that repair or reinforce the ruptured side to ipsilateral structures, then immobilize in extension 6-10 weeks, followed by an intense course of therapy. Cause of deformity can be[for full text, please go to the a.m. URL], 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

Published
2020
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36. The MLL recombinome of acute leukemias

Author

Meyer, C, Schneider, B, Jakob, S, Strehl, S, Attarbaschi, A, Schnittger, S, Schoch, C, Jansen, M W J C, van Dongen, J J M, den Boer, M L, Pieters, R, Ennas, M-G, Angelucci, E, Koehl, U, Greil, J, Griesinger, F, zur Stadt, U, Eckert, C, Szczepański, T, Niggli, F K, Schäfer, B W, Kempski, H, Brady, H J M, Zuna, J, Trka, J, Nigro, L L, Biondi, A, Delabesse, E, Macintyre, E, Stanulla, M, Schrappe, M, Haas, O A, Burmeister, T, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2006
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37. Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial

Author

Attarbaschi, A., Mann, G., Zimmermann, M., Bader, P., Barisone, E., Basso, G., Biondi, A., Cario, G., Cazzaniga, G., Colombini, A., Flotho, C., Kuhlen, M., Lang, P., Lauten, M., Linderkamp, C., Locatelli, Franco, Lo Nigro, L., Moricke, A., Niggli, F., Panzer-Grumayer, R., Parasole, R., Peters, C., Caterina Putti, M., Rizzari, C., Suttorp, M., Valsecchi, M. G., Conter, V., Schrappe, M., Locatelli F. (ORCID:0000-0002-7976-3654), Attarbaschi, A., Mann, G., Zimmermann, M., Bader, P., Barisone, E., Basso, G., Biondi, A., Cario, G., Cazzaniga, G., Colombini, A., Flotho, C., Kuhlen, M., Lang, P., Lauten, M., Linderkamp, C., Locatelli, Franco, Lo Nigro, L., Moricke, A., Niggli, F., Panzer-Grumayer, R., Parasole, R., Peters, C., Caterina Putti, M., Rizzari, C., Suttorp, M., Valsecchi, M. G., Conter, V., Schrappe, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2020

38. The data acquisition system for the ANTARES neutrino telescope

Author

Aguilar, J.A., Albert, A., Ameli, F., Anghinolfi, M., Anton, G., Anvar, S., Aslanides, E., Aubert, J.-J., Barbarito, E., Basa, S., Battaglieri, M., Becherini, Y., Bellotti, R., Beltramelli, J., Bertin, V., Bigi, A., Billault, M., Blaes, R., de Botton, N., Bouwhuis, M.C., Bradbury, S.M., Bruijn, R., Brunner, J., Burgio, G.F., Busto, J., Cafagna, F., Caillat, L., Calzas, A., Capone, A., Caponetto, L., Carmona, E., Carr, J., Cartwright, S.L., Castel, D., Castorina, E., Cavasinni, V., Cecchini, S., Ceres, A., Charvis, P., Chauchot, P., Chiarusi, T., Circella, M., Colnard, C., Compère, C., Coniglione, R., Cottini, N., Coyle, P., Cuneo, S., Cussatlegras, A.-S., Damy, G., van Dantzig, R., De Marzo, C., Dekeyser, I., Delagnes, E., Denans, D., Deschamps, A., Dessages-Ardellier, F., Destelle, J.-J., Dinkespieler, B., Distefano, C., Donzaud, C., Drogou, J.-F., Druillole, F., Durand, D., Ernenwein, J.-P., Escoffier, S., Falchini, E., Favard, S., Feinstein, F., Ferry, S., Festy, D., Fiorello, C., Flaminio, V., Galeotti, S., Gallone, J.-M., Giacomelli, G., Girard, N., Gojak, C., Goret, Ph., Graf, K., Hallewell, G., Harakeh, M.N., Hartmann, B., Heijboer, A., Heine, E., Hello, Y., Hernández-Rey, J.J., Hößl, J., Hoffman, C., Hogenbirk, J., Hubbard, J.R., Jaquet, M., Jaspers, M., de Jong, M., Jouvenot, F., Kalantar-Nayestanaki, N., Kappes, A., Karg, T., Karkar, S., Katz, U., Keller, P., Kok, H., Kooijman, P., Kopper, C., Korolkova, E.V., Kouchner, A., Kretschmer, W., Kruijer, A., Kuch, S., Kudryavstev, V.A., Lachartre, D., Lafoux, H., Lagier, P., Lahmann, R., Lamanna, G., Lamare, P., Languillat, J.C., Laschinsky, H., Le Guen, Y., Le Provost, H., Le Van Suu, A., Legou, T., Lim, G., Lo Nigro, L., Lo Presti, D., Loehner, H., Loucatos, S., Louis, F., Lucarelli, F., Lyashuk, V., Marcelin, M., Margiotta, A., Masullo, R., Mazéas, F., Mazure, A., McMillan, J.E., Megna, R., Melissas, M., Migneco, E., Milovanovic, A., Mongelli, M., Montaruli, T., Morganti, M., Moscoso, L., Musumeci, M., Naumann, C., Naumann-Godo, M., Niess, V., Olivetto, C., Ostasch, R., Palanque-Delabrouille, N., Payre, P., Peek, H., Petta, C., Piattelli, P., Pineau, J.-P., Poinsignon, J., Popa, V., Pradier, T., Racca, C., Randazzo, N., van Randwijk, J., Real, D., van Rens, B., Réthoré, F., Rewiersma, P., Riccobene, G., Rigaud, V., Ripani, M., Roca, V., Roda, C., Rolin, J.F., Romita, M., Rose, H.J., Rostovtsev, A., Roux, J., Ruppi, M., Russo, G.V., Salesa, F., Salomon, K., Sapienza, P., Schmitt, F., Schuller, J.-P., Shanidze, R., Sokalski, I., Spona, T., Spurio, M., van der Steenhoven, G., Stolarczyk, T., Streeb, K., Stubert, D., Sulak, L., Taiuti, M., Tamburini, C., Tao, C., Terreni, G., Thompson, L.F., Valdy, P., Valente, V., Vallage, B., Venekamp, G., Verlaat, B., Vernin, P., de Vita, R., de Vries, G., van Wijk, R., de Witt Huberts, P., Wobbe, G., de Wolf, E., Yao, A.-F., Zaborov, D., Zaccone, H., Zornoza, J.D., and Zúñiga, J.

Published
2007
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42. The MLL recombinome of acute leukemias in 2013

Author

Meyer, C, Hofmann, J, Burmeister, T, Gröger, D, Park, T S, Emerenciano, M, Pombo de Oliveira, M, Renneville, A, Villarese, P, Macintyre, E, Cavé, H, Clappier, E, Mass-Malo, K, Zuna, J, Trka, J, De Braekeleer, E, De Braekeleer, M, Oh, S H, Tsaur, G, Fechina, L, van der Velden, V HJ, van Dongen, J JM, Delabesse, E, Binato, R, Silva, M LM, Kustanovich, A, Aleinikova, O, Harris, M H, Lund-Aho, T, Juvonen, V, Heidenreich, O, Vormoor, J, Choi, W WL, Jarosova, M, Kolenova, A, Bueno, C, Menendez, P, Wehner, S, Eckert, C, Talmant, P, Tondeur, S, Lippert, E, Launay, E, Henry, C, Ballerini, P, Lapillone, H, Callanan, M B, Cayuela, J M, Herbaux, C, Cazzaniga, G, Kakadiya, P M, Bohlander, S, Ahlmann, M, Choi, J R, Gameiro, P, Lee, D S, Krauter, J, Cornillet-Lefebvre, P, Te Kronnie, G, Schäfer, B W, Kubetzko, S, Alonso, C N, zur Stadt, U, Sutton, R, Venn, N C, Izraeli, S, Trakhtenbrot, L, Madsen, H O, Archer, P, Hancock, J, Cerveira, N, Teixeira, M R, Lo Nigro, L, Möricke, A, Stanulla, M, Schrappe, M, Sedék, L, Szczepański, T, Zwaan, C M, Coenen, E A, van den Heuvel-Eibrink, M M, Strehl, S, Dworzak, M, Panzer-Grümayer, R, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2013
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43. First results of the Instrumentation Line for the deep-sea ANTARES neutrino telescope

Author

Aguilar, J.A., Albert, A., Ameli, F., Anghinolfi, M., Anton, G., Anvar, S., Aslanides, E., Aubert, J.-J., Barbarito, E., Basa, S., Battaglieri, M., Becherini, Y., Bellotti, R., Beltramelli, J., Bertin, V., Bigi, A., Billault, M., Blaes, R., de Botton, N., Bouwhuis, M.C., Bradbury, S.M., Bruijn, R., Brunner, J., Burgio, G.F., Busto, J., Cafagna, F., Caillat, L., Calzas, A., Capone, A., Caponetto, L., Carmona, E., Carr, J., Cartwright, S.L., Castel, D., Castorina, E., Cavasinni, V., Cecchini, S., Ceres, A., Charvis, P., Chauchot, P., Chiarusi, T., Circella, M., Colnard, C., Compère, C., Coniglione, R., Cottini, N., Coyle, P., Cuneo, S., Cussatlegras, A.-S., Damy, G., van Dantzig, R., De Marzo, C., Dekeyser, I., Delagnes, E., Denans, D., Deschamps, A., Dessages-Ardellier, F., Destelle, J.-J., Dinkespieler, B., Distefano, C., Donzaud, C., Drogou, J.-F., Druillole, F., Durand, D., Ernenwein, J.-P., Escoffier, S., Falchini, E., Favard, S., Feinstein, F., Ferry, S., Festy, D., Fiorello, C., Flaminio, V., Galeotti, S., Gallone, J.-M., Giacomelli, G., Girard, N., Gojak, C., Goret, Ph., Graf, K., Hallewell, G., Harakeh, M.N., Hartmann, B., Heijboer, A., Heine, E., Hello, Y., Hernández-Rey, J.J., Hößl, J., Hoffman, C., Hogenbirk, J., Hubbard, J.R., Jaquet, M., Jaspers, M., de Jong, M., Jouvenot, F., Kalantar-Nayestanaki, N., Kappes, A., Karg, T., Karkar, S., Katz, U., Keller, P., Kok, H., Kooijman, P., Kopper, C., Korolkova, E.V., Kouchner, A., Kretschmer, W., Kruijer, A., Kuch, S., Kudryavstev, V.A., Lachartre, D., Lafoux, H., Lagier, P., Lahmann, R., Lamanna, G., Lamare, P., Languillat, J.C., Laschinsky, H., Le Guen, Y., Le Provost, H., Le Van Suu, A., Legou, T., Lim, G., Lo Nigro, L., Lo Presti, D., Loehner, H., Loucatos, S., Louis, F., Lucarelli, F., Lyashuk, V., Marcelin, M., Margiotta, A., Masullo, R., Mazéas, F., Mazure, A., McMillan, J.E., Megna, R., Melissas, M., Migneco, E., Milovanovic, A., Mongelli, M., Montaruli, T., Morganti, M., Moscoso, L., Musumeci, M., Naumann, C., Naumann-Godo, M., Niess, V., Olivetto, C., Ostasch, R., Palanque-Delabrouille, N., Payre, P., Peek, H., Petta, C., Piattelli, P., Pineau, J.-P., Poinsignon, J., Popa, V., Pradier, T., Racca, C., Randazzo, N., van Randwijk, J., Real, D., van Rens, B., Réthoré, F., Rewiersma, P., Riccobene, G., Rigaud, V., Ripani, M., Roca, V., Roda, C., Rolin, J.F., Romita, M., Rose, H.J., Rostovtsev, A., Roux, J., Ruppi, M., Russo, G.V., Salesa, F., Salomon, K., Sapienza, P., Schmitt, F., Schuller, J.-P., Shanidze, R., Sokalski, I., Spona, T., Spurio, M., van der Steenhoven, G., Stolarczyk, T., Streeb, K., Stubert, D., Sulak, L., Taiuti, M., Tamburini, C., Tao, C., Terreni, G., Thompson, L.F., Valdy, P., Valente, V., Vallage, B., Venekamp, G., Verlaat, B., Vernin, P., de Vita, R., de Vries, G., van Wijk, R., de Witt Huberts, P., Wobbe, G., de Wolf, E., Yao, A.-F., Zaborov, D., Zaccone, H., Zornoza, J.D., and Zúñiga, J.

Published
2006
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49. Transmission of light in deep sea water at the site of the A ntares neutrino telescope

Author

Aguilar, J.A., Albert, A., Amram, P., Anghinolfi, M., Anton, G., Anvar, S., Ardellier-Desages, F.E., Aslanides, E., Aubert, J-J., Azoulay, R., Bailey, D., Basa, S., Battaglieri, M., Becherini, Y., Bellotti, R., Beltramelli, J., Bertin, V., Billault, M., Blaes, R., Blanc, F., Bland, R.W., de Botton, N., Boulesteix, J., Bouwhuis, M.C., Brooks, C.B., Bradbury, S.M., Bruijn, R., Brunner, J., Bugeon, F., Burgio, G.F., Cafagna, F., Calzas, A., Caponetto, L., Carmona, E., Carr, J., Cartwright, S.L., Cecchini, S., Charvis, P., Circella, M., Colnard, C., Compère, C., Croquette, J., Cooper, S., Coyle, P., Cuneo, S., Damy, G., van Dantzig, R., Deschamps, A., Marzo, C. De, Destelle, J.-J., Vita, R. De, Dinkelspiler, B., Dispau, G., Drougou, J.-F., Druillole, F., Engelen, J., Favard, S., Feinstein, F., Ferry, S., Festy, D., Fopma, J., Fuda, J.-L., Gallone, J.-M., Giacomelli, G., Girard, N., Goret, P., Gournay, J.-F., Hallewell, G., Hartmann, B., Heijboer, A., Hello, Y., Hernández-Rey, J.J., Herrouin, G., Hößl, J., Hoffmann, C., Hubbard, J.R., Jaquet, M., de Jong, M., Jouvenot, F., Kappes, A., Karg, T., Karkar, S., Karolak, M., Katz, U., Keller, P., Kooijman, P., Korolkova, E.V., Kouchner, A., Kretschmer, W., Kudryavtsev, V.A., Lafoux, H., Lagier, P., Lamare, P., Languillat, J.-C., Laubier, L., Legou, T., Guen, Y. Le, Provost, H. Le, Van Suu, A. Le, Nigro, L. Lo, Presti, D. Lo, Loucatos, S., Louis, F., Lyashuk, V., Magnier, P., Marcelin, M., Margiotta, A., Maron, C., Massol, A., Mazéas, F., Mazeau, B., Mazure, A., McMillan, J.E., Michel, J.-L., Millot, C., Milovanovic, A., Montanet, F., Montaruli, T., Morel, J.-P., Moscoso, L., Nezri, E., Niess, V., Nooren, G.J., Ogden, P., Olivetto, C., Palanque-Delabrouille, N., Payre, P., Petta, C., Pineau, J.-P., Poinsignon, J., Popa, V., Potheau, R., Pradier, T., Racca, C., Randazzo, N., Real, D., van Rens, B.A.P., Réthoré, F., Ripani, M., Roca-Blay, V., Romeyer, A., Rollin, J.-F., Romita, M., Rose, H.J., Rostovtsev, A., Ruppi, M., Russo, G.V., Sacquin, Y., Saouter, S., Schuller, J.-P., Schuster, W., Sokalski, I., Suvorova, O., Spooner, N.J.C., Spurio, M., Stolarczyk, T., Stubert, D., Taiuti, M., Thompson, L.F., Tilav, S., Usik, A., Valdy, P., Vallage, B., Vaudaine, G., Vernin, P., Virieux, J., Vladimirsky, E., de Vries, G., de Witt Huberts, P., de Wolf, E., Zaborov, D., Zaccone, H., Zakharov, V., Zavatarelli, S., de Zornoza, J.D., and Zúñiga, J.

Published
2005
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50. Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope

Author

Aguilar, J.A., Albert, A., Ameli, F., Amram, P., Anghinolfi, M., Anton, G., Anvar, S., Ardellier-Desages, F.E., Aslanides, E., Aubert, J.-J., Bailey, D., Basa, S., Battaglieri, M., Becherini, Y., Bellotti, R., Beltramelli, J., Bertin, V., Billault, M., Blaes, R., Blanc, F., de Botton, N., Boulesteix, J., Bouwhuis, M.C., Brooks, C.B., Bradbury, S.M., Bruijn, R., Brunner, J., Burgio, G.F., Cafagna, F., Calzas, A., Capone, A., Caponetto, L., Carmona, E., Carr, J., Cartwright, S.L., Castorina, E., Cavasinni, V., Cecchini, S., Charvis, P., Circella, M., Colnard, C., Compère, C., Coniglione, R., Cooper, S., Coyle, P., Cuneo, S., Damy, G., van Dantzig, R., Deschamps, A., De Marzo, C., Denans, D., Destelle, J.-J., De Vita, R., Dinkelspiler, B., Distefano, C., Drogou, J.-F., Druillole, F., Engelen, J., Ernenwein, J.-P., Falchini, E., Favard, S., Feinstein, F., Ferry, S., Festy, D., Flaminio, V., Fopma, J., Fuda, J.-L., Gallone, J.-M., Giacomelli, G., Girard, N., Goret, P., Graf, K., Hallewell, G., Hartmann, B., Heijboer, A., Hello, Y., Hernández-Rey, J.J., Herrouin, G., Hößl, J., Hoffmann, C., Hubbard, J.R., Jaquet, M., de Jong, M., Jouvenot, F., Kappes, A., Karg, T., Karkar, S., Karolak, M., Katz, U., Keller, P., Kooijman, P., Korolkova, E.V., Kouchner, A., Kretschmer, W., Kuch, S., Kudryavtsev, V.A., Lafoux, H., Lagier, P., Lahmann, R., Lamare, P., Languillat, J.-C., Laschinsky, H., Laubier, L., Legou, T., Le Guen, Y., Le Provost, H., Le Van Suu, A., Lo Nigro, L., Lo Presti, D., Loucatos, S., Louis, F., Lyashuk, V., Marcelin, M., Margiotta, A., Maron, C., Massol, A., Masullo, R., Mazéas, F., Mazure, A., McMillan, J.E., Migneco, E., Millot, C., Milovanovic, A., Montanet, F., Montaruli, T., Morel, J.-P., Morganti, M., Moscoso, L., Musumeci, M., Naumann, C., Naumann-Godo, M., Nezri, E., Niess, V., Nooren, G.J., Ogden, P., Olivetto, C., Palanque-Delabrouille, N., Papaleo, R., Payre, P., Petta, C., Piattelli, P., Pineau, J.-P., Poinsignon, J., Popa, V., Potheau, R., Pradier, T., Racca, C., Raia, G., Randazzo, N., Real, D., van Rens, B.A.P., Réthoré, F., Riccobene, G., Rigaud, V., Ripani, M., Roca-Blay, V., Rolin, J.-F., Romita, M., Rose, H.J., Rostovtsev, A., Ruppi, M., Russo, G.V., Sacquin, Y., Salesa, F., Salomon, K., Saouter, S., Sapienza, P., Shanidze, R., Schuller, J.-P., Schuster, W., Sokalski, I., Spurio, M., Stolarczyk, T., Stubert, D., Taiuti, M., Thompson, L.F., Tilav, S., Valdy, P., Valente, V., Vallage, B., Vernin, P., Virieux, J., de Vries, G., de Witt Huberts, P., de Wolf, E., Zaborov, D., Zaccone, H., Zakharov, V., Zornoza, J.D., and Zúñiga, J.

Published
2005
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