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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. Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS

Author

Kuendgen, A., Nomdedeu, M., Tuechler, H., Garcia-Manero, G., Komrokji, R. S., Sekeres, M. A., Della Porta, M. G., Cazzola, M., DeZern, A. E., Roboz, G. J., Steensma, D. P., Van de Loosdrecht, A. A., Schlenk, R. F., Grau, J., Calvo, X., Blum, S., Pereira, A., Valent, P., Costa, D., Giagounidis, A., Xicoy, B., Döhner, H., Platzbecker, U., Pedro, C., Lübbert, M., Oiartzabal, I., Díez-Campelo, M., Cedena, M. T., Machherndl-Spandl, S., López-Pavía, M., Baldus, C. D., Martinez-de-Sola, M., Stauder, R., Merchan, B., List, A., Ganster, C., Schroeder, T., Voso, M. T., Pfeilstöcker, M., Sill, H., Hildebrandt, B., Esteve, J., Nomdedeu, B., Cobo, F., Haas, R., Sole, F., Germing, U., Greenberg, P. L., Haase, D., and Sanz, G.

Published
2021
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4. 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

6. Natural history of Ras‐associated autoimmune leukoproliferative disorder: A 20‐year follow‐up of a NRAS‐mutated patient excluding a malignant progression.

Author

Rivalta, B., Attardi, E., Cifaldi, C., Rosti, V., Pacillo, L., Hajrullaj, H., Di Cesare, S., Amodio, D., Algeri, M., Luciani, M., Barzaghi, F., Finocchi, A., Di Matteo, G., Aiuti, A., Locatelli, F., Voso, M. T., Palumbo, G., and Cancrini, C.

Subjects
NATURAL history, AUTOIMMUNE diseases, PELVIC inflammatory disease, MONONUCLEAR leukocytes, CORD blood transplantation
Abstract

This article explores the natural history of Ras-associated autoimmune leukoproliferative disorder (RALD), a rare condition caused by mutations in the NRAS or KRAS genes. RALD is characterized by lymphadenopathy, splenomegaly, persistent leucocytosis, and autoimmune symptoms. The article discusses the challenges in diagnosing and monitoring RALD patients, as some may develop juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML), while others may experience spontaneous improvement. The article presents a case study of a 22-year-old male with RALD, providing a clinical history and a detailed analysis of his immune profile. The study emphasizes the importance of exploring somatic gene variants in patients with specific immunological profiles and suggests that an integrated approach combining clinical parameters, functional assays, and longitudinal assessment of additional mutations may help predict disease progression. The findings contribute to the understanding of RALD and may enhance monitoring and treatment strategies for patients with this rare condition. [Extracted from the article]

Published
2024
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7. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Author

Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, Sauta, Elisabetta, Robin, Marie, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Zhao, Lin-Pierre, Caballero Berrocal, Juan Carlos, Sala, Claudia, Maggioni, Giulia, Bernardi, Massimo, Di Grazia, Carmen, Vago, Luca, Rivoli, Giulia, Borin, Lorenza, D'Amico, Saverio, Tentori, Cristina Astrid, Ubezio, Marta, Campagna, Alessia, Russo, Antonio, Mannina, Daniele, Lanino, Luca, Chiusolo, Patrizia, Giaccone, Luisa, Voso, Maria Teresa, Riva, Marta, Oliva, Esther Natalie, Zampini, Matteo, Riva, Elena, Nibourel, Olivier, Bicchieri, Marilena, Bolli, Niccolo', Rambaldi, Alessandro, Passamonti, Francesco, Savevski, Victor, Santoro, Armando, Germing, Ulrich, Kordasti, Shahram, Santini, Valeria, Diez-Campelo, Maria, Sanz, Guillermo, Sole, Francesc, Kern, Wolfgang, Platzbecker, Uwe, Ades, Lionel, Fenaux, Pierre, Haferlach, Torsten, Castellani, Gastone, Della Porta, Matteo Giovanni, Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Della Porta, M, Sauta, Elisabetta, Robin, Marie, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Zhao, Lin-Pierre, Caballero Berrocal, Juan Carlos, Sala, Claudia, Maggioni, Giulia, Bernardi, Massimo, Di Grazia, Carmen, Vago, Luca, Rivoli, Giulia, Borin, Lorenza, D'Amico, Saverio, Tentori, Cristina Astrid, Ubezio, Marta, Campagna, Alessia, Russo, Antonio, Mannina, Daniele, Lanino, Luca, Chiusolo, Patrizia, Giaccone, Luisa, Voso, Maria Teresa, Riva, Marta, Oliva, Esther Natalie, Zampini, Matteo, Riva, Elena, Nibourel, Olivier, Bicchieri, Marilena, Bolli, Niccolo', Rambaldi, Alessandro, Passamonti, Francesco, Savevski, Victor, Santoro, Armando, Germing, Ulrich, Kordasti, Shahram, Santini, Valeria, Diez-Campelo, Maria, Sanz, Guillermo, Sole, Francesc, Kern, Wolfgang, Platzbecker, Uwe, Ades, Lionel, Fenaux, Pierre, Haferlach, Torsten, Castellani, Gastone, and Della Porta, Matteo Giovanni

Abstract

Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. Conclusion: IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevan

Published
2023

8. A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Author

Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, Matteo G Della Porta, Maggioni, G, Bersanelli, M, Travaglino, E, Alfonso Piérola, A, Kasprzak, A, Sangerman Montserrat, A, Sauta, E, Sala, C, Matteuzzi, T, Meggendorfer, M, Gnocchi, M, Zhao, L, Astrid Tentori, C, Nachtkamp, K, Dall'Olio, D, Mosca, E, Ubezio, M, Campagna, A, Russo, A, Rivoli, G, Bernardi, M, Borin, L, Teresa Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Saba, E, D'Amico, S, Lanino, L, Tinterri, B, Re, F, Bicchieri, M, Giordano, L, Angelotti, G, Morandini, P, Sophie Kubasch, A, Passamonti, F, Rambaldi, A, Savevski, V, Santoro, A, A van de Loosdrecht, A, Brogi, A, Santini, V, Kordasti, S, Sanz, G, Sole, F, Gattermann, N, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, Germing, U, Diez-Campelo, M, G Della Porta, M, Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Piérola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin-Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez-Campelo, and Matteo G Della Porta

Abstract

BACKGROUND: Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. METHODS: In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Düsseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. FINDINGS: The study included 7792 (58·7%) men and 5492 (41·3%) women. 10 906 (82·1%) patients were White, and race was not reported for 2378 (17·9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0·0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0·0062 in the IWG-PM cohort; IDH2 p<0·0001 in EuroMDS vs p=0·042 in IWG-PM; TET2 p=0·031 vs p=0·035; U2AF1 p=0·033 vs p<0·0001) and mutations in two genes were enriched in women (DNMT3A p<0·000

Published
2023

9. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Author

Sauta, E., Robin, M., Bersanelli, M., Travaglino, E., Meggendorfer, M., Zhao, L. -P., Caballero Berrocal, J. C., Sala, C., Maggioni, G., Bernardi, M., Di Grazia, C., Vago, L., Rivoli, G., Borin, L., D'Amico, S., Tentori, C. A., Ubezio, M., Campagna, A., Russo, A., Mannina, D., Lanino, L., Chiusolo, Patrizia, Giaccone, L., Voso, Maria Teresa, Riva, M., Oliva, E. N., Zampini, M., Riva, E., Nibourel, O., Bicchieri, M., Bolli, N., Rambaldi, A., Passamonti, F., Savevski, V., Santoro, A., Germing, U., Kordasti, S., Santini, V., Diez-Campelo, M., Sanz, G., Sole, F., Kern, W., Platzbecker, U., Ades, L., Fenaux, P., Haferlach, T., Castellani, G., Della Porta, M. G., Chiusolo P. (ORCID:0000-0002-1355-1587), Voso M. T., Sauta, E., Robin, M., Bersanelli, M., Travaglino, E., Meggendorfer, M., Zhao, L. -P., Caballero Berrocal, J. C., Sala, C., Maggioni, G., Bernardi, M., Di Grazia, C., Vago, L., Rivoli, G., Borin, L., D'Amico, S., Tentori, C. A., Ubezio, M., Campagna, A., Russo, A., Mannina, D., Lanino, L., Chiusolo, Patrizia, Giaccone, L., Voso, Maria Teresa, Riva, M., Oliva, E. N., Zampini, M., Riva, E., Nibourel, O., Bicchieri, M., Bolli, N., Rambaldi, A., Passamonti, F., Savevski, V., Santoro, A., Germing, U., Kordasti, S., Santini, V., Diez-Campelo, M., Sanz, G., Sole, F., Kern, W., Platzbecker, U., Ades, L., Fenaux, P., Haferlach, T., Castellani, G., Della Porta, M. G., Chiusolo P. (ORCID:0000-0002-1355-1587), and Voso M. T.

Abstract

PURPOSEMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.METHODSA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.RESULTSIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.CONCLUSIONIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may

Published
2023

10. Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System

Author

Della Porta, M G, Jackson, C H, Alessandrino, E P, Rossi, M, Bacigalupo, A, van Lint, M T, Bernardi, M, Allione, B, Bosi, A, Guidi, S, Santini, V, Malcovati, L, Ubezio, M, Milanesi, C, Todisco, E, Voso, M T, Musto, P, Onida, F, Iori, A P, Cerretti, R, Grillo, G, Molteni, A, Pioltelli, P, Borin, L, Angelucci, E, Oldani, E, Sica, S, Pascutto, C, Ferretti, V, Santoro, A, Bonifazi, F, Cazzola, M, and Rambaldi, A

Published
2017
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11. Pre-transplant persistence of minimal residual disease does not contraindicate allogeneic stem cell transplantation for adult patients with acute myeloid leukemia

Author

Buccisano, F, Maurillo, L, Piciocchi, A, Del Principe, M I, Picardi, A, Cerretti, R, Cudillo, L, De Angelis, G, Sarlo, C, Cefalo, M, Ditto, C, Di Veroli, A, Mariotti, B, Nasso, D, De Bellis, E, Del Poeta, G, Voso, M T, Sconocchia, G, Lo Coco, F, Arcese, W, Amadori, S, and Venditti, A

Published
2017
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14. 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

15. ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol

Author

Buccisano, F, Palmieri, R, Piciocchi, A, Arena, V, Candoni, A, Melillo, L, Calafiore, V, Cairoli, R, de Fabritiis, P, Storti, G, Salutari, P, Lanza, F, Martinelli, G, Luppi, M, Capria, S, Maurillo, L, Del Principe, M, Paterno, G, Consalvo, M, Ottone, T, Lavorgna, S, Voso, M, Fazi, P, Vignetti, M, Arcese, W, Venditti, A, Del Principe, MI, Consalvo, MAI, Voso, MT, Buccisano, F, Palmieri, R, Piciocchi, A, Arena, V, Candoni, A, Melillo, L, Calafiore, V, Cairoli, R, de Fabritiis, P, Storti, G, Salutari, P, Lanza, F, Martinelli, G, Luppi, M, Capria, S, Maurillo, L, Del Principe, M, Paterno, G, Consalvo, M, Ottone, T, Lavorgna, S, Voso, M, Fazi, P, Vignetti, M, Arcese, W, Venditti, A, Del Principe, MI, Consalvo, MAI, and Voso, MT

Abstract

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P, .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P 5 .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P 5 .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. Th

Published
2022

16. 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

17. P987: A DIFFERENT BALANCE IN OXIDATIVE STRESS RESPONSE IN CALR AND JAK2 MUTATED MYELOFIBROSIS PATIENTS CORRELATES WITH CLINICAL OUTCOME

Author

Genovese, E., primary, Mirabile, M., additional, Rontauroli, S., additional, Sartini, S., additional, Fantini, S., additional, Tavernari, L., additional, Maccaferri, M., additional, Guglielmelli, P., additional, Bianchi, E., additional, Parenti, S., additional, Carretta, C., additional, Mallia, S., additional, Castellano, S., additional, Colasante, C., additional, Balliu, M., additional, Bartalucci, N., additional, Palmieri, R., additional, Ottone, T., additional, Mora, B., additional, Potenza, L., additional, Passamonti, F., additional, Voso, M. T., additional, Luppi, M., additional, Vannucchi, A. M., additional, Tagliafico, E., additional, and Manfredini, R., additional

Published
2022
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18. S130: NPM1 MUTATED AML: IMPACT OF CO-MUTATIONAL PATTERNS - RESULTS OF THE EUROPEAN HARMONY ALLIANCE

Author

Hernández-Sánchez, A., primary, Villaverde-Ramiro, Á., additional, Martínez Elicegui, J., additional, González, T., additional, Benner, A., additional, Sträng, E., additional, Castellani, G., additional, Heckman, C. A., additional, Versluis, J., additional, Abáigar, M., additional, Sobas, M., additional, Azibeiro, R., additional, Tur, L., additional, Valk, P. J., additional, Metzeler, K. H., additional, Ayala, R., additional, Dall’Olio, D., additional, Tettero, J., additional, Martínez-López, J., additional, Dombret, H., additional, Pratcorona, M., additional, Damm, F., additional, Mills, K. I., additional, Mayer, J., additional, Thiede, C., additional, Voso, M. T., additional, Sanz, G. F., additional, Calado, F., additional, Döhner, K., additional, Gaidzik, V. I., additional, Heuser, M., additional, Haferlach, T., additional, Turki, A. T., additional, Reinhardt, D., additional, Villoria Medina, R., additional, van Speybroeck, M., additional, Schulze-Rath, R., additional, Barbus, M., additional, Butler, J. E., additional, Hernández Rivas, J. M., additional, Huntly, B. J., additional, Ossenkoppele, G. J., additional, Döhner, H., additional, and Bullinger, L., additional

Published
2022
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19. P1000: INCREASED PLASMA LEVELS OF LNCRNAS ARE POTENTIAL PROGNOSTIC BIOMARKERS IN MYELOFIBROSIS

Author

Sartini, S., primary, Fantini, S., additional, Rontauroli, S., additional, Mirabile, M., additional, Bianchi, E., additional, Badii, F., additional, Maccaferri, M., additional, Guglielmelli, P., additional, Ottone, T., additional, Palmieri, R., additional, Genovese, E., additional, Carretta, C., additional, Parenti, S., additional, Mallia, S., additional, Tavernari, L., additional, Salvadori, C., additional, Gesullo, F., additional, Maccari, C., additional, Zizza, M., additional, Grande, A., additional, Salmoiraghi, S., additional, Mora, B., additional, Potenza, L., additional, Rosti, V., additional, Passamonti, F., additional, Rambaldi, A., additional, Voso, M. T., additional, Mecucci, C., additional, Tagliafico, E., additional, Luppi, M., additional, Vannucchi, A. M., additional, and Manfredini, R., additional

Published
2022
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20. 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
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22. Function of PU.1 (Spi-1), C/EBP, and AML1 in Early Myelopoiesis: Regulation of Multiple Myeloid CSF Receptor Promoters

Author

Zhang, D.-E., Hohaus, S., Voso, M. T., Chen, H.-M., Smith, L. T., Hetherington, C. J., Tenen, D. G., Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wolff, Linda, editor, and Perkins, Archibald S., editor

Published
1996
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23. 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

24. Bone Marrow Microenvironment Involvement in t-MN: Focus on Mesenchymal Stem Cells.

Author

Falconi, Giulia, Galossi, E., Hajrullaj, H., Fabiani, E., and Voso, M. T.

Subjects
MESENCHYMAL stem cells, BONE marrow, HEMATOPOIETIC stem cells, GENE expression, IMMUNOSENESCENCE, GENE expression profiling
Abstract

Therapy-related myeloid neoplasms (t-MN) are a late complication of cytotoxic therapy (CT) used in the treatment of both malignant and non-malignant diseases. Historically, t-MN has been considered to be a direct consequence of DNA damage induced in normal hematopoietic stem or progenitor cells (HSPC) by CT. However, we now know that treatment-induced mutations in HSC are not the only players involved in t-MN development, but additional factors may contribute to the onset of t-MN. One of the known drivers involved in this field is the bone marrow microenvironment (BMM) and, in particular, bone marrow mesenchymal stem cells (BM-MSC), whose role in t-MN pathogenesis is the topic of this mini-review. BM-MSCs, physiologically, support HSC maintenance, self-renewal, and differentiation through hematopoietic-stromal interactions and the production of cytokines. In addition, BM-MSCs maintain the stability of the BM immune microenvironment and reduce the damage caused to HSC by stress stimuli. In the t-MN context, chemo/radiotherapy may induce damage to the BM-MSC and likewise alter BM-MSC functions by promoting pro-inflammatory response, clonal selection and/or the production of factors that may favor malignant hematopoiesis. Over the last decade, it has been shown that BM-MSC isolated from patients with de novo and therapy-related MN exhibit decreased proliferative and clonogenic capacity, altered morphology, increased senescence, defective osteogenic differentiation potential, impaired immune-regulatory properties, and reduced ability to support HSC growth and differentiation, as compared to normal BM-MSC. Although the understanding of the genetic and gene expression profile associated with ex vivoexpanded t-MN-MSCs remains limited and debatable, its potential role in prognostic and therapeutic terms is acting as a flywheel of attraction for many researchers. [ABSTRACT FROM AUTHOR]

Published
2023
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25. 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

26. Treatment of Philadelphia-negative myeloproliferative neoplasms in accelerated/blastic phase with azacytidine. Clinical results and identification of prognostic factors

Author

Andriani, A, Elli, E, Trape, G, Villiva, N, Fianchi, L, Di Veroli, A, Niscola, P, Centra, A, Anaclerico, B, Montanaro, G, Martini, V, Aroldi, A, Carmosino, I, Voso, M, Breccia, M, Montanaro, M, Foa, R, Latagliata, R, Andriani A., Elli E., Trape G., Villiva N., Fianchi L., Di Veroli A., Niscola P., Centra A., Anaclerico B., Montanaro G., Martini V., Aroldi A., Carmosino I., Voso M. T., Breccia M., Montanaro M., Foa R., Latagliata R., Andriani, A, Elli, E, Trape, G, Villiva, N, Fianchi, L, Di Veroli, A, Niscola, P, Centra, A, Anaclerico, B, Montanaro, G, Martini, V, Aroldi, A, Carmosino, I, Voso, M, Breccia, M, Montanaro, M, Foa, R, Latagliata, R, Andriani A., Elli E., Trape G., Villiva N., Fianchi L., Di Veroli A., Niscola P., Centra A., Anaclerico B., Montanaro G., Martini V., Aroldi A., Carmosino I., Voso M. T., Breccia M., Montanaro M., Foa R., and Latagliata R.

Abstract

There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P =.908). These three subgroups as “responders” having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P =.001) Only female gender was significant for both achievement of response (.010) and OS duration (P =.002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders.

Published
2019

28. New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia

Author

Ianniello, Z, Sorci, M, Ginistrelli, L, Iaiza, A, Marchioni, M, Tito, C, Capuano, E, Masciarelli, S, Ottone, T, Attrotto, C, Rizzo, M, Franceschini, L, de Pretis, S, Voso, M, Pelizzola, M, Fazi, F, Fatica, A, Ianniello Z, Sorci M, Ginistrelli LC, Iaiza A, Marchioni M, Tito C, Capuano E, Masciarelli S, Ottone T, Attrotto C, Rizzo M, Franceschini L, de Pretis S, Voso MT, Pelizzola M, Fazi F, Fatica A, Ianniello, Z, Sorci, M, Ginistrelli, L, Iaiza, A, Marchioni, M, Tito, C, Capuano, E, Masciarelli, S, Ottone, T, Attrotto, C, Rizzo, M, Franceschini, L, de Pretis, S, Voso, M, Pelizzola, M, Fazi, F, Fatica, A, Ianniello Z, Sorci M, Ginistrelli LC, Iaiza A, Marchioni M, Tito C, Capuano E, Masciarelli S, Ottone T, Attrotto C, Rizzo M, Franceschini L, de Pretis S, Voso MT, Pelizzola M, Fazi F, and Fatica A

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

Published
2021

29. Characteristics and outcome of acute myeloid leukemia with uncommon retinoic acid receptor-alpha (RARA) fusion variants

Author

Cicconi, L., Testi, A. M., Montesinos, P., Rego, E., Zhu, H. H., Takahashi, H., Dworzak, M., Estey, E., Schwarer, A., Esteve, J., Annibali, O., Castelli, R., Mirabile, M., Angelini, M., Lazarevic, V., Kumar, J., Avvisati, G., Gurnari, C., Locatelli, Franco, Voso, M. T., Sanz, M. A., Lo-Coco, F., Abla, O., Locatelli F. (ORCID:0000-0002-7976-3654), Cicconi, L., Testi, A. M., Montesinos, P., Rego, E., Zhu, H. H., Takahashi, H., Dworzak, M., Estey, E., Schwarer, A., Esteve, J., Annibali, O., Castelli, R., Mirabile, M., Angelini, M., Lazarevic, V., Kumar, J., Avvisati, G., Gurnari, C., Locatelli, Franco, Voso, M. T., Sanz, M. A., Lo-Coco, F., Abla, O., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2021

30. 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

31. New insight into the catalytic -dependent and -independent roles of METTL3 in sustaining aberrant translation in chronic myeloid leukemia

Author

Ianniello, Z., Sorci, M., Ceci Ginistrelli, L., Iaiza, A., Marchioni, M., Tito, C., Capuano, E., Masciarelli, Silvia, Ottone, T., Attrotto, C., Rizzo, M., Franceschini, L., de Pretis, S., Voso, M. T., Pelizzola, M., Fazi, F., Fatica, A., Masciarelli S., Ianniello, Z., Sorci, M., Ceci Ginistrelli, L., Iaiza, A., Marchioni, M., Tito, C., Capuano, E., Masciarelli, Silvia, Ottone, T., Attrotto, C., Rizzo, M., Franceschini, L., de Pretis, S., Voso, M. T., Pelizzola, M., Fazi, F., Fatica, A., and Masciarelli S.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m(6)A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

Published
2021

35. 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

41. Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS

Author

Kuendgen, A., primary, Nomdedeu, M., additional, Tuechler, H., additional, Garcia-Manero, G., additional, Komrokji, R. S., additional, Sekeres, M. A., additional, Della Porta, M. G., additional, Cazzola, M., additional, DeZern, A. E., additional, Roboz, G. J., additional, Steensma, D. P., additional, Van de Loosdrecht, A. A., additional, Schlenk, R. F., additional, Grau, J., additional, Calvo, X., additional, Blum, S., additional, Pereira, A., additional, Valent, P., additional, Costa, D., additional, Giagounidis, A., additional, Xicoy, B., additional, Döhner, H., additional, Platzbecker, U., additional, Pedro, C., additional, Lübbert, M., additional, Oiartzabal, I., additional, Díez-Campelo, M., additional, Cedena, M. T., additional, Machherndl-Spandl, S., additional, López-Pavía, M., additional, Baldus, C. D., additional, Martinez-de-Sola, M., additional, Stauder, R., additional, Merchan, B., additional, List, A., additional, Ganster, C., additional, Schroeder, T., additional, Voso, M. T., additional, Pfeilstöcker, M., additional, Sill, H., additional, Hildebrandt, B., additional, Esteve, J., additional, Nomdedeu, B., additional, Cobo, F., additional, Haas, R., additional, Sole, F., additional, Germing, U., additional, Greenberg, P. L., additional, Haase, D., additional, and Sanz, G., additional

Published
2020
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43. 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

44. Lenalidomide treatment of myelodysplastic syndromes with chromosome 5q deletion: Results from the National Registry of the Italian Drug Agency

Author

Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., Visani, G., Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., and Visani, G.

Subjects
Oncology, Myeloid, Male, Group B, Immunologic Factor, 0302 clinical medicine, Retrospective Studie, hemic and lymphatic diseases, del(5q), Prospective Studies, Registries, Prospective cohort study, Hematology, Leukemia, registry study, Standard treatment, Remission Induction, General Medicine, Middle Aged, lenalidomide, myelodysplastic syndromes, Aged, Chromosomes, Human, Pair 5, Disease Progression, Female, Humans, Immunologic Factors, Italy, Karyotyping, Lenalidomide, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Retrospective Studies, Thalidomide, Chromosome Deletion, 030220 oncology & carcinogenesis, Pair 5, medicine.drug, Human, medicine.medical_specialty, Myelodysplastic Syndrome, Acute, Chromosomes, NO, 03 medical and health sciences, Internal medicine, medicine, business.industry, Myelodysplastic syndromes, Retrospective cohort study, medicine.disease, Settore MED/15, Prospective Studie, business, 030215 immunology
Abstract

Objective The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution. Methods MORE study was an observational, non-interventional, multi-centre, retrospective and prospective study. Cases were recruited from 45 Haematological Centres throughout Italy. Data were collected from the Italian National Registry for Lenalidomide administration and supplemented by a MORE data form. Results Data from 190/213 patients were analysed. In all, 149 had been diagnosed by conventional cytogenetics (GROUP A) and 41 only by FISH (GROUP B). Overall erythroid response was obtained in 92.8% of cases. Overall cytogenetic remission was achieved in 22.6% of cases. Disease progression occurred in 15.6% of cases. Clonal cytogenetic evolution characterised progression to AML but not to higher risk MDS. Conclusions Erythroid response to Lenalidomide was similar in MDS with isolated del(5q) and with del(5q) plus one anomaly. Progression to AML or higher risk MDS showed different cytogenetic features.

Published
2018

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