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173 results on '"Divona, M."'

2. Risk-adapted MRD-directed therapy for young adults with acute myeloid leukemia: 6-year update of the GIMEMA AML1310 trial

Author

Venditti, A, Piciocchi, A, Candoni, A, Arena, V, Palmieri, R, Fili, C, Carella, A, Calafiore, V, Cairoli, R, De Fabritiis, P, Storti, G, Salutari, P, Lanza, F, Martinelli, G, Curti, A, Luppi, M, Ingrosso, C, Martelli, M, Cuneo, A, Albano, F, Mule, A, Tafuri, A, Cudillo, L, Tieghi, A, Fracchiolla, N, Capelli, D, Trisolini, S, Alati, C, La Sala, E, Maurillo, L, Del Principe, M, Consalvo, M, Divona, M, Ottone, T, Cerretti, R, Sconocchia, G, Voso, M, Fazi, P, Vignetti, M, Buccisano, F, Venditti A., Piciocchi A., Candoni A., Arena V., Palmieri R., Fili C., Carella A. M., Calafiore V., Cairoli R., De Fabritiis P., Storti G., Salutari P., Lanza F., Martinelli G., Curti A., Luppi M., Ingrosso C., Martelli M. P., Cuneo A., Albano F., Mule A., Tafuri A., Cudillo L., Tieghi A., Fracchiolla N. S., Capelli D., Trisolini S. M., Alati C., La Sala E., Maurillo L., Del Principe M. I., Consalvo M. A. I., Divona M. D., Ottone T., Cerretti R., Sconocchia G., Voso M. T., Fazi P., Vignetti M., Buccisano F., Venditti, A, Piciocchi, A, Candoni, A, Arena, V, Palmieri, R, Fili, C, Carella, A, Calafiore, V, Cairoli, R, De Fabritiis, P, Storti, G, Salutari, P, Lanza, F, Martinelli, G, Curti, A, Luppi, M, Ingrosso, C, Martelli, M, Cuneo, A, Albano, F, Mule, A, Tafuri, A, Cudillo, L, Tieghi, A, Fracchiolla, N, Capelli, D, Trisolini, S, Alati, C, La Sala, E, Maurillo, L, Del Principe, M, Consalvo, M, Divona, M, Ottone, T, Cerretti, R, Sconocchia, G, Voso, M, Fazi, P, Vignetti, M, Buccisano, F, Venditti A., Piciocchi A., Candoni A., Arena V., Palmieri R., Fili C., Carella A. M., Calafiore V., Cairoli R., De Fabritiis P., Storti G., Salutari P., Lanza F., Martinelli G., Curti A., Luppi M., Ingrosso C., Martelli M. P., Cuneo A., Albano F., Mule A., Tafuri A., Cudillo L., Tieghi A., Fracchiolla N. S., Capelli D., Trisolini S. M., Alati C., La Sala E., Maurillo L., Del Principe M. I., Consalvo M. A. I., Divona M. D., Ottone T., Cerretti R., Sconocchia G., Voso M. T., Fazi P., Vignetti M., and Buccisano F.

Published
2024

3. Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial–mesenchymal transition pathways

Author

Ottone, T, Silvestrini, G, Piazza, R, Travaglini, S, Gurnari, C, Marchesi, F, Nardozza, A, Fabiani, E, Attardi, E, Guarnera, L, Divona, M, Ricci, P, Irno Consalvo, M, Ienzi, S, Arcese, R, Biagi, A, Fiori, L, Novello, M, Mauriello, A, Venditti, A, Anemona, L, Voso, M, Ottone T., Silvestrini G., Piazza R., Travaglini S., Gurnari C., Marchesi F., Nardozza A. M., Fabiani E., Attardi E., Guarnera L., Divona M., Ricci P., Irno Consalvo M. A., Ienzi S., Arcese R., Biagi A., Fiori L., Novello M., Mauriello A., Venditti A., Anemona L., Voso M. T., Ottone, T, Silvestrini, G, Piazza, R, Travaglini, S, Gurnari, C, Marchesi, F, Nardozza, A, Fabiani, E, Attardi, E, Guarnera, L, Divona, M, Ricci, P, Irno Consalvo, M, Ienzi, S, Arcese, R, Biagi, A, Fiori, L, Novello, M, Mauriello, A, Venditti, A, Anemona, L, Voso, M, Ottone T., Silvestrini G., Piazza R., Travaglini S., Gurnari C., Marchesi F., Nardozza A. M., Fabiani E., Attardi E., Guarnera L., Divona M., Ricci P., Irno Consalvo M. A., Ienzi S., Arcese R., Biagi A., Fiori L., Novello M., Mauriello A., Venditti A., Anemona L., and Voso M. T.

Abstract

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial–mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication. [Figure not available: see fulltext.]

Published
2023

8. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, Amadori S, Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, and Amadori S

Published
2021

9. CD99 as a novel therapeutic target on leukemic progenitor cells in FLT3-ITDmut AML

Author

Travaglini, S., Ottone, T., Angelini, D. F., Fiori, V., Dominici, S., Noguera, N. I., Sniegocka, M., Antonelli, S., Irno Consalvo, M. A., De Bardi, M., Banella, C., Divona, M., Marchesi, F., Masciarelli, Silvia, Fazi, F., Pieraccioli, M., Palmieri, R., De Angelis, G., Buccisano, F., Venditti, A., Battistini, L., Magnani, M., Voso, M. T., Masciarelli S., Travaglini, S., Ottone, T., Angelini, D. F., Fiori, V., Dominici, S., Noguera, N. I., Sniegocka, M., Antonelli, S., Irno Consalvo, M. A., De Bardi, M., Banella, C., Divona, M., Marchesi, F., Masciarelli, Silvia, Fazi, F., Pieraccioli, M., Palmieri, R., De Angelis, G., Buccisano, F., Venditti, A., Battistini, L., Magnani, M., Voso, M. T., and Masciarelli S.

Abstract

Acute Myeloid Leukemia with FLT3 internal tandem duplication mutations (FLT3-ITDmut AML) is an aggressive leukemia character- ized by heterogeneous genetic landscape [1]. Despite significant advances in AML therapy, the relapse rate remains high, due to the emergence of resistant clones, possibly involving leukemic stem cells (LSCs) [2]. This highlights the unmet need for deeper understanding of the molecular and immunophenotypic land- scape of LSCs in FLT3-ITDmut AML. We previously identified a population of leukemic precursor cells (LPCs), present at the time of initial AML diagnosis, characterized by the CD34/CD123/CD25/ CD99+ immunophenotype, and predictive for FLT3-ITDmut positivity [3]. In particular, these cells overexpress CD99 antigen, which may represent a target for monoclonal antibody (mAb) treatment [4]

Published
2022

10. P434: MITOCONDRIAL MCL1 REGULATES LEUKEMIC CELLS METABOLISM VIA DIRECT INTERACTION WITH HEXOKINASE II. METABOLIC SIGNATURE AT ONSET PREDICTS OVERALL SURVIVAL IN AMLS’ PATIENTS

Author

Noguera, N. I., primary, Catalano, G., additional, Zaza, A., additional, Banella, C., additional, Ottone, T., additional, Pelosi, E., additional, Travaglini, S., additional, Divona, M., additional, Del Principe, M. I., additional, Buccisano, F., additional, Maurillo, L., additional, Amatuna, E., additional, Testa, U., additional, Venditti, A., additional, and Voso, M. T., additional

Published
2022
Full Text
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11. Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial

Author

Buccisano, F, Palmieri, R, Piciocchi, A, Arena, V, Maurillo, L, Del Principe, M, Paterno, G, Irno-Consalvo, M, Ottone, T, Divona, M, Conti, C, Fraboni, D, Lavorgna, S, Arcese, W, Voso, Mt, and Venditti, A

Subjects
measurable residual disease, Acute myeloid leukemia, immunophenotyping, minimal residual disease, Acute myeloid leukemia, minimal residual disease, measurable residual disease, immunophenotyping, Settore MED/15
Published
2022

13. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2020

14. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M. T., Cucci, R., Messina, M., Santoro, A., Divona, M., Albano, F., Ottaviani, E., Roberta Bertorelle, Guerrasio, A., Gottardi, E., Izzo, B., Tarantini, G., Scardocci, A., Siragusa, S., Forghieri, F., Cairoli, R., Cambo, B., Vallisa, D., Venditti, A., Ferrara, F., Mannina, D., Cilloni, D., La Sala, E., Piciocchi, A., Falini, B., Pane, F., Saglio, G., Vignetti, M., Amadori, S., Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, and Amadori, S

Subjects
Hematology
Published
2021

17. Early and sensitive detection of PML-A216V mutation by droplet digital PCR in ATO-resistant acute promyelocytic leukemia

Author

Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Travaglini, S, Falconi, G, Hasan, S, Venditti, A, Arcese, W, Voso, M, Lo-Coco, F, Alfonso V, Iaccarino L, Ottone T, Cicconi L, Lavorgna S, Divona M, Cairoli R, Cristiano A, Ciardi C, Travaglini S, Falconi G, Hasan SK, Venditti A, Arcese W, Voso MT, Lo-Coco F., Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Travaglini, S, Falconi, G, Hasan, S, Venditti, A, Arcese, W, Voso, M, Lo-Coco, F, Alfonso V, Iaccarino L, Ottone T, Cicconi L, Lavorgna S, Divona M, Cairoli R, Cristiano A, Ciardi C, Travaglini S, Falconi G, Hasan SK, Venditti A, Arcese W, Voso MT, and Lo-Coco F.

Published
2019

18. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2019

24. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, and Lo-Coco, F

Subjects
Hematology
Published
2019

25. SENSITIVE AND EARLY DETECTION OF THE PML-A216V MUTATION BY DROPLET DIGITAL PCR IN ARSENIC TRIOXIDE RESISTANT ACUTE PROMYELOCYTIC LEUKEMIA

Author

Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Chiusolo, P, Venditti, A, Arcese, W, Voso, M, Lo Coco, F, Alfonso V, Iaccarino L, Ottone T, Cicconi L, Lavorgna S, Divona M, Cairoli R, Cristiano A, Ciardi C, Chiusolo P, Venditti A, Arcese W, Voso MT, Lo Coco F, Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Chiusolo, P, Venditti, A, Arcese, W, Voso, M, Lo Coco, F, Alfonso V, Iaccarino L, Ottone T, Cicconi L, Lavorgna S, Divona M, Cairoli R, Cristiano A, Ciardi C, Chiusolo P, Venditti A, Arcese W, Voso MT, and Lo Coco F

Published
2018

26. Characterization ofFLT3-ITD(mut)acute myeloid leukemia: molecular profiling of leukemic precursor cells

Author

Travaglini, S, Angelini, DF, Alfonso, V, Guerrera, G, Lavorgna, S, Divona, M, Nardozza, AM, Consalvo, MI, Fabiani, E, De Bardi, M, Neri, B, Forghieri, F, Marchesi, F, Paterno, G, Cerretti, R, Barragan, E, Fiori, V, Dominici, S, Del Principe, MI, Venditti, A, Battistini, L, Arcese, W, Lo-Coco, F, Voso, MT, and Ottone, T

Subjects
body regions, psychological phenomena and processes
Abstract

Acute myeloid leukemia (AML) withFLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts forFLT3-ITD-positivity. The aim of this study was to characterize the distribution ofFLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture ofFLT3-ITD(mut)AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients withFLT3-ITD(mut)AML (n = 12). A higherFLT3-ITD(mut)load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/-,CD25-,CD99low/-) (p = 0.0005) and mononuclear cells (MNCs) (p < 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higherFLT3-ITD(mut)burden was also observed in LPCs of AML patients with a smallFLT3-ITD(mut)clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows thatFLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target inFLT3-ITD(mut)AML.

Published
2020

28. SENSITIVE AND EARLY DETECTION OF THE PML-A216V MUTATION BY DROPLET DIGITAL PCR IN ARSENIC TRIOXIDE RESISTANT ACUTE PROMYELOCYTIC LEUKEMIA

Author

Alfonso, V., Iaccarino, L., Ottone, T., Cicconi, L., Lavorgna, S., Divona, M., Cairoli, R., Cristiano, A., Ciardi, C., Patrizia Chiusolo, Venditti, A., Arcese, W., Voso, M. T., Lo Coco, F., Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Chiusolo, P, Venditti, A, Arcese, W, Voso, M, and Lo Coco, F

Subjects
hematology
Published
2018

29. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: Final results of the randomized Italian-German APL0406 trial

Author

Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F., Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, and Lo-Coco F.

Abstract

Purpose: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods: The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results: Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively (P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion: These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Published
2017

31. PS1011 MEASURABLE RESIDUAL DISEASE BY MULTIPARAMETRIC FLOW-CYTOMETRY IS A RELIABLE TOOL FOR RISK-STRATIFICATION OF FLT3-MUTATED AML PATIENTS

Author

Palmieri, R., primary, Maurillo, L., additional, Principe, M.I. Del, additional, Veroli, A. Di, additional, Paterno, G., additional, Bellis, E. De, additional, Cerretti, R., additional, Angelis, G. De, additional, Mariotti, B., additional, Ottone, T., additional, Divona, M., additional, Lavorgna, S., additional, Consalvo, M.A. Irno, additional, Conti, C., additional, Attrotto, C., additional, Fraboni, D., additional, Voso, M.T., additional, Amadori, S., additional, Coco, F. Lo, additional, Arcese, W., additional, Venditti, A., additional, and Buccisano, F., additional

Published
2019
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32. Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML.

Author

Masciarelli, Silvia, Capuano, E, Ottone, T, Divona, M, Lavorgna, S, Liccardo, F, Śniegocka, M, Travaglini, S, Noguera, Ni, Picardi, A, Petrozza, V, Fatica, A, Tamagnone, Luca, Voso, M, Lo Coco, F, Fazi, F1., Masciarelli S, Tamagnone L (ORCID:0000-0002-2884-7946), Masciarelli, Silvia, Capuano, E, Ottone, T, Divona, M, Lavorgna, S, Liccardo, F, Śniegocka, M, Travaglini, S, Noguera, Ni, Picardi, A, Petrozza, V, Fatica, A, Tamagnone, Luca, Voso, M, Lo Coco, F, Fazi, F1., Masciarelli S, and Tamagnone L (ORCID:0000-0002-2884-7946)

Abstract

Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation.

Published
2019

34. Retinoic acid sensitizes acute myeloid leukemia cells to ER stress

Author

Masciarelli, Silvia, Capuano, Ernestina, Bellissimo, Teresa, Ottone, T., Divona, M. D., Lo Coco, F., and Fazi, Francesco

Subjects
AML, ER stress, RA, ATO, neoplasms
Abstract

Acute myeloid leukemia (AML) is caused by the blockade of hematopoietic myeloid precursors at different stages of differentiation. A subtype of AML, acute promyelocytic leukemia (APL), is a paradigm of differentiation therapy since retinoic acid (RA) is able to induce leukemic blast terminal differentiation leading to cure rates exceeding 80% when administered in combination with chemotherapy. Although APL patients refractory to RA or who relapsed are very effectively treated with arsenic trioxide (ATO) in combination with RA, the elevated costs limit its use in developing countries and in first line therapy so that RA plus chemotherapy currently remain the standard of care (1, 2). Most importantly non-APL acute myeloid leukemia do not respond to RA indicating the need for novel strategies to sensitize AML cells to RA. Here we show that RA-triggered differentiation of APL cells induces endoplasmic reticulum (ER) stress slightly activating the unfolded protein response (UPR). This is sufficient to render leukemic cell lines and human primary blasts very sensitive to doses of ER stress inducing drugs, like tunicamycin (Tm), that are not toxic for the same cells in the absence of RA or for most cell types. Furthermore we observed that low doses of Tm, even in the absence of RA, are sufficient to strongly increase ATO toxicity. Indeed both RA-sensitive and RA-resistant APL cell lines resulted sensitive to Tm-ATO combined treatment at low doses of ATO that are ineffective in the absence of ER stress. The use of inhibitors targeting specific UPR branches indicate that the Protein Kinase RNA-like Endoplasmic Reticulum kinase (PERK) pathway protects differentiating APL cells from ER stress rendering it an interesting therapeutic molecular target. Finally, we extended our observations in a non-APL model, assessing that RA sensitize the non-APL cell line HL60 to ER stress. Altogether our data indicate ER stress as a possible target for designing novel combination therapeutic strategies in AML. Contribution of AIRC (StG 4841) and FILAS-RU-2014-1020 to FF was greatly appreciated., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

Published
2017
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35. Retinoic acid and arsenic trioxide sensitize acute promyelocytic leukemia cells to ER stress

Author

Masciarelli, Silvia, Capuano, E., Ottone, T., Divona, M., De Panfilis, S., Banella, C., Noguera, N. I., Picardi, A., Fontemaggi, G., Blandino, G., Lo-Coco, F., Fazi, Francesco, Masciarelli S., Masciarelli, Silvia, Capuano, E., Ottone, T., Divona, M., De Panfilis, S., Banella, C., Noguera, N. I., Picardi, A., Fontemaggi, G., Blandino, G., Lo-Coco, F., Fazi, Francesco, and Masciarelli S.

Abstract

Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity. Indeed, in the presence of ER stress, ATO efficiently induced apoptosis in RA-sensitive and RA-resistant APL cell lines, at doses ineffective in the absence of ER stress. Our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML.

Published
2018

37. The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia

Author

Sanarico, A G, primary, Ronchini, C, additional, Croce, A, additional, Memmi, E M, additional, Cammarata, U A, additional, De Antoni, A, additional, Lavorgna, S, additional, Divona, M, additional, Giacò, L, additional, Melloni, G E M, additional, Brendolan, A, additional, Simonetti, G, additional, Martinelli, G, additional, Mancuso, P, additional, Bertolini, F, additional, Coco, F Lo, additional, Melino, G, additional, Pelicci, P G, additional, and Bernassola, F, additional

Published
2017
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40. PML-RAR alpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy

Author

Cicconi, L, Divona, M, Ciardi, C, Ottone, T, Ferrantini, A, Lavorgna, S, Alfonso, V, Paoloni, F, Piciocchi, A, Avvisati, G, Ferrara, F, Di Bona, E, Albano, F, Breccia, M, Cerqui, E, Sborgia, M, Kropp, Mg, Santoro, A, Levis, A, Sica, Simona, Amadori, S, Voso, Mt, Mandelli, F, Lo-Coco, F, Sica, S (ORCID:0000-0003-2426-3465), Cicconi, L, Divona, M, Ciardi, C, Ottone, T, Ferrantini, A, Lavorgna, S, Alfonso, V, Paoloni, F, Piciocchi, A, Avvisati, G, Ferrara, F, Di Bona, E, Albano, F, Breccia, M, Cerqui, E, Sborgia, M, Kropp, Mg, Santoro, A, Levis, A, Sica, Simona, Amadori, S, Voso, Mt, Mandelli, F, Lo-Coco, F, and Sica, S (ORCID:0000-0003-2426-3465)

Abstract

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-alpha (PML-RAR alpha) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARa transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P = 0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RAR alpha transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P = 0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

Published
2016

41. Clustering of genomic breakpoints at the MLL locus in therapy-related acute leukemia with t(4;11)(q21;q23)

Author

Hasan, Sk, Barba, Gianluca, Metzler, M, Divona, M, Ottone, T, Cicconi, L, Falini, Brunangelo, Mecucci, Cristina, and Lo Coco, F.

Subjects
Biphenotypic, Topoisomerase Inhibitors, Molecular Sequence Data, Translocation, Breast Neoplasms, Acute, Chromosomes, Translocation, Genetic, Chromosome Breakpoints, Genetic, Leukemia, Promyelocytic, Acute, Antibiotics, Ductal, Humans, Breast, Pair 11, Epirubicin, Promyelocytic, Leukemia, Antibiotics, Antineoplastic, Base Sequence, Carcinoma, Ductal, Breast, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 4, Female, Idarubicin, Leukemia, Biphenotypic, Acute, Middle Aged, Multigene Family, Genetic Loci, Carcinoma, Antineoplastic, Pair 4, Settore MED/15 - Malattie del Sangue, Human
Abstract

Genomic characterization of translocation breakpoints is relevant to identify possible mechanisms underlying their origin. The consistent association of anthracylines (e.g., epirubicin and idarubicin) in inducing therapy-related acute leukemias (t-AL) with mixed lineage leukemia (MLL) gene rearrangement suggests that MLL translocations are causative events for t-AL. Using asymmetric multiplex PCR strategy followed by direct DNA sequencing, we characterized the genomic breakpoints of the MLL and AFF1 genes in two patients who developed t-AL with t(4;11)(q21;q23). Chemotherapeutic treatment of the primary disease in both patients included topoisomerase II (topo II) targeting agents. In one case, the MLL breakpoint was located in intron 9 at nucleotide position chr11:118354284 while the AFF1 breakpoint was in intron 3 at nucleotide position chr4:87992070. The breakpoint junction sequences revealed an insertion of two nucleotides at the MLL-AFF1 junction. In the other patient, the MLL breakpoint was located in intron 11 at nucleotide position chr11:118359130-32 and the AFF1 break was in intron 3 at nucleotide position chr4:87996215-17. The MLL breakpoint found in the latter patient was identical to that of two previously reported cases, strongly suggesting the presence of a preferential site of DNA cleavage in the presence of topo II inhibitor. In addition, microhomologies at the breakpoint junctions were indicative of DNA repair by the non-homologous end joining (NHEJ) pathway. This study further supports the evidence that MLL breakpoints in therapy-related acute leukemia with MLL-AFF1 are clustered in the telomeric half of the breakpoint cluster region that contains topo II recognition sites.

Published
2013

43. Identification of emerging FLT3 ITD-positive clones during clinical remission and kinetics of disease relapse in acute myeloid leukaemia with mutated nucleophosmin

Author

Ottone, Zaza, T, S, Divona, M, Hasan, S, Lavorgna, S, Laterza, S, Cicconi, L, Panetta, P, Di Giandomenico, J, Cittadini, M, Ciardi, C, Montefusco, E, Franchi, A, Annino, L, Venditti, A, Amadori, S, and LO COCO, F

Subjects
Oncology, FLT3 Internal Tandem Duplication, Adult, Male, NPM1, medicine.medical_specialty, Myeloid, Gene Dosage, Somatic evolution in cancer, law.invention, law, Recurrence, hemic and lymphatic diseases, Internal medicine, Gene Duplication, Gene duplication, medicine, Humans, Polymerase chain reaction, Retrospective Studies, business.industry, Induction chemotherapy, Nuclear Proteins, hemic and immune systems, Hematology, Induction Chemotherapy, Middle Aged, medicine.disease, body regions, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, fms-Like Tyrosine Kinase 3, embryonic structures, Immunology, Mutation, Female, business, Settore MED/15 - Malattie del Sangue, Nucleophosmin, psychological phenomena and processes
Abstract

FLT3 internal tandem duplication (ITD) mutations are frequently detected at diagnosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and predict unfavourable outcome. FLT3 ITD is an unstable aberration and may be lost or acquired at relapse. Recent whole genome sequencing studies have suggested that FLT3 ITD(+)ve AML relapse may evolve from small subclones undetectable at diagnosis by routine polymerase chain reaction (PCR). We developed a patient-specific real-time quantitative-PCR (RQ-PCR) to implement FLT3 ITD detection in six AML patients whose blasts carried wild-type FLT3 at diagnosis and who relapsed with FLT3 ITD by routine PCR. Patient-specific forward primers were designed after cloning and sequencing the FLT3 ITD in each case. The assay allowed retrospective detection of FLT3 ITD in diagnostic samples of 4/6 cases and to establish the kinetics of clonal evolution preceding relapse. After conventional chemotherapy, all patients had early relapse despite having been classified as NPM1(+)ve/FLT3 ITD(-)ve at presentation, with shorter remissions being observed in four patients re-classified as FLT3 ITD(+)ve by the new assay. Notably, FLT3 ITD clone became detectable by conventional PCR in three patients tested during remission after initial treatment. Our data underscore the need of identifying low FLT3 ITD levels, which are probably associated with relapse in otherwise good prognosis CN-AML.

Published
2012

44. Molecular characterization of paediatric idiopathic hypereosinophilia

Author

Rapanotti, M, Caruso, R, Ammatuna, E, Zaza, S, Trotta, L, Divona, M, Cicconi, L, Funaro, D, Federici, G, Amadori, S, De Rossi, G, and LO COCO, F

Subjects
Gene Rearrangement, Male, Lymphoma, B-Cell, Adolescent, Infant, lymphoma, B-cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, preschool, Immunophenotyping, prognosis, adolescent, male, infant, female, child, preschool, gene rearrangement, hypereosinophilic syndrome, precursor cell lymphoblastic leukemia-lymphoma, humans, follow-up studies, lymphoma, B-cell, child, immunophenotyping, immunoglobulin heavy chains, Child, Preschool, Hypereosinophilic Syndrome, Humans, Female, Child, Immunoglobulin Heavy Chains, Settore MED/15 - Malattie del Sangue, Follow-Up Studies
Abstract

The hypereosinophilic syndromes (HES) include a group of heterogeneous diseases characterized by the persistent increase of the number of eosinophils in blood and bone marrow. Few cases of paediatric hypereosinophilia (pHES) have been described in the literature. Early identification of pHES that may evolve towards a lymphomyeloproliferative disease is relevant in light of prognostic and therapeutic implications. Molecular features of 10 pHES patients were analysed at presentation and during their clinical course, including analysis of BCR-ABL1 and FIP1L1/PDGFRA fusion genes, quantitation of WT1 gene copy number and clonality of T-cell receptor (TCR) and immunoglobulin heavy chain (IGH). All patients had normal karyotype and germline TCR configuration. Five children showed IGH clonality at presentation: of these, two developed a B non-Hodgkin lymphoma and a B-lineage acute lymphocytic leukaemia at six and 12 months respectively, two spontaneously reverted to a polyclonal IGH profile during the follow-up, and the last one persisted with pHES without B-clonal evolution after 19 months. One patient had a PDGFRA/FIP1L1 fusion and achieved hematologic and molecular remission after imatinib therapy. IGH rearrangement was observed to be a frequent molecular feature of pHES and may precede B-cell clonal expansion and evolution into B-cell malignancies in children.

Published
2010

45. Molecular remission in advanced acute promyelocytic leukaemia after treatment with the oral synthetic retinoid Tamibarotene

Author

Di Veroli, A, Ramadan, S, Divona, M, Cudillo, L, Giannì, L, Wieland, S, Giannotti, F, Mirabile, M, Arcese, W, and LO COCO, F

Subjects
Recurrence, Leukemia, Promyelocytic, Acute, Antineoplastic Agents, Hematopoietic Stem Cell Transplantation, Female, Tetrahydronaphthalenes, Adult, Humans, Benzoates, Promyelocytic, Leukemia, Acute, Settore MED/15 - Malattie del Sangue
Published
2010

47. Identification of a potential 'Hotspot' DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation

Author

Ottone, T, Hasan, Sk, Montefusco, E, Curzi, P, Mays, An, Chessa, L, Ferrari, A, Conte, E, Noguera, Ni, Lavorgna, S, Ammatuna, E, Divona, M, Bovetti, K, Amadori, S, Grimwade, D, and LO COCO, F

Subjects
Myeloid, Male, genomic DNA, sequence analysis, polymerase chain reaction, complementary DNA, multiple sclerosis, granulocyte colony stimulating factor, gene targeting, cytarabine, In Situ Hybridization, Oncogene Proteins, Leukemia, adult, article, Middle Aged, acute granulocytic leukemia, leukemia cell, priority journal, Core Binding Factor Alpha 2 Subunit, Cytogenetic Analysis, transcription factor RUNX1, intron, DNA sequence, Translocation, Acute, Type II, mitoxantrone, Fluorescence, Databases, Genetic, human genome, DNA, fludarabine, case report, chromosome translocation, gene, gene fusion, gene identification, gene translocation, human, male, nucleotide sequence, RUNXI gene, Databases, Genetic, DNA Topoisomerases, Type II, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myeloid, Acute, Mitoxantrone, Multiple Sclerosis, Oncogene Proteins, Fusion, Phosphoproteins, Repressor Proteins, Sequence Analysis, DNA, Translocation, Genetic, Tumor Suppressor Proteins, Fusion, Neoplastic, Gene Expression Regulation, Settore MED/15 - Malattie del Sangue, DNA Topoisomerases
Published
2009

48. ACCURACY AND PRECISION OF RESULTS AFTER IMPLEMENTATION OF INTERNATIONAL SCALE TO EVALUATE MINIMAL RESIDUAL DISEASE IN CHRONIC MYELOID LEUKEMIA PATIENTS COORDINATED ON BEHALF OF GIMEMA-CML WP

Author

Quarantelli, F, Izzo, B, Amabile, M, Gottardi, E, Albano, F, Spinelli, O, Vigneri, P, Gozzini, A, Garuti, A, Pezzetti, L, Colnaghi, F, Monne, M, Santoro, A, Bernasconi, P, Di Ianni, M, Donati, M, Giannini, B, Mammi’, C, Diverio, D, Divona, M. D., De Matteis, G, Rossi, G, Culurgioni, F, Minervini, M, Galimberti, Sara, Nicci, C, Saglio, G, Martinelli, G, and Pane, F.

Published
2009

49. The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia

Author

Sanarico, A G, Ronchini, C, Croce, A, Memmi, E M, Cammarata, U A, De Antoni, A, Lavorgna, S, Divona, M, Giacò, L, Melloni, G E M, Brendolan, A, Simonetti, G, Martinelli, G, Mancuso, P, Bertolini, F, Coco, F Lo, Melino, G, Pelicci, P G, and Bernassola, F

Abstract

The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared with haematopoietic cells from healthy donors. We show that WWP1 inactivation severely impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation induces the accumulation of its protein substrate p27Kip1, which ultimately contributes to G0/G1cell cycle arrest of AML blasts. In addition, WWP1 depletion triggers the autophagy signalling and reduces survival of leukaemic cells. Collectively, our findings provide molecular insights into the anti-cancer potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker and druggable target in AML.

Published
2018
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50. Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells

Author

Iosue, I., Quaranta, R., Masciarelli, Silvia, Fontemaggi, G., Batassa, E. M., Bertolami, C., Ottone, T., Divona, M., Salvatori, B., Padula, F., Fatica, A., Lo-Coco, F., Nervi, C., Fazi, F., Masciarelli S., Iosue, I., Quaranta, R., Masciarelli, Silvia, Fontemaggi, G., Batassa, E. M., Bertolami, C., Ottone, T., Divona, M., Salvatori, B., Padula, F., Fatica, A., Lo-Coco, F., Nervi, C., Fazi, F., and Masciarelli S.

Abstract

MicroRNAs are key regulators of many biological processes, including cell differentiation. These small RNAs exert their function assembled in the RNA-induced silencing complexes (RISCs), where members of Argonaute (Ago) family of proteins provide a unique platform for target recognition and gene silencing. Here, by using myeloid cell lines and primary blasts, we show that Ago2 has a key role in human monocytic cell fate determination and in LPS-induced inflammatory response of 1,25-dihydroxyvitamin D3 (D3)-treated myeloid cells. The silencing of Ago2 impairs the D3-dependent miR-17-5p/20a/106a, miR-125b and miR-155 downregulation, the accumulation of their translational targets AML1, VDR and C/EBPb and monocytic cell differentiation. Moreover, we show that Ago2 is recruited on miR-155 host gene promoter and on the upstream region of an overlapping antisense lncRNA, determining their epigenetic silencing, and miR-155 downregulation. These findings highlight Ago2 as a new factor in myeloid cell fate determination in acute myeloid leukemia cells. © 2013 Macmillan Publishers Limited All rights reserved.

Published
2013

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