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128 results on '"Pelosini M"'

1. Primary Mediastinal B‐cell Lymphoma, a nationwide real‐life retrospective study from Fondazione Italiana Linfomi (FIL)

Author

Iannitto, E., primary, Balzarotti, M., additional, Martelli, M., additional, Zinzani, P., additional, Tucci, A., additional, Di Rocco, A., additional, Cavallo, F., additional, Usai, S. V., additional, Guidetti, A., additional, Ravano, E., additional, Merli, F., additional, Botto, B., additional, Pelosini, M., additional, Tecchio, C., additional, Spina, M., additional, Derenzini, E., additional, Finotto, S., additional, Mola, B., additional, Pinto, A., additional, Zanni, E., additional, Battistini, R., additional, Hohaus, S., additional, Dogliotti, I., additional, Gini, G., additional, Zilioli, V. R., additional, De Lorenzo, S., additional, Dodero, A., additional, Broccoli, A., additional, Maggi, A., additional, Mannarella, C., additional, Chiarenza, A., additional, Pastore, D., additional, Cascavilla, N., additional, Musto, P., additional, Stelitano, C., additional, Di Raimondo, F., additional, Di Renzo, N., additional, Liberati, A. M., additional, Salerno, M., additional, Scalone, R., additional, Nassi, L., additional, Patti, C., additional, Polizzi, V., additional, Guarini, A., additional, Amato, G., additional, Ciccone, G., additional, Evangelista, A., additional, Lo Presti, F., additional, La Porta, A., additional, Mannina, D., additional, Calogero, R. D., additional, Musso, M., additional, and Consoli, U., additional

Published
2023
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2. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Author

Clavero, E., Sanchez-Maldonado, J.M., Macauda, A., Horst, R. ter, Sampaio-Marques, B., Jurczyszyn, A., Clay-Gilmour, A., Stein, A., Hildebrandt, M.A., Weinhold, N., Buda, G., García-Sanz, R., Tomczak, W., Vogel, U., Jerez, A., Zawirska, D., Wątek, M., Hofmann, J.N., Landi, S., Spinelli, J.J., Butrym, A., Kumar, A., Martínez-López, J., Galimberti, S., Sarasquete, M.E., Subocz, E., Iskierka-Jażdżewska, E., Giles, G.G., Rybicka-Ramos, M., Kruszewski, M., Abildgaard, N., Verdejo, F.G., Sánchez Rovira, P., Silva Filho, M.I. da, Kadar, K., Razny, M., Cozen, W., Pelosini, M., Jurado, M., Bhatti, P., Dudzinski, M., Druzd-Sitek, A., Orciuolo, E., Li, Y., Norman, A.D., Zaucha, J.M., Reis, R.M., Markiewicz, M., Rodríguez Sevilla, J.J., Andersen, V., Jamroziak, K., Hemminki, K., Berndt, S.I., Rajkumar, V., Mazur, G., Kumar, S.K., Ludovico, P., Nagler, A., Chanock, S.J., Dumontet, C., Machiela, M.J., Varkonyi, J., Camp, N.J., Ziv, E., Vangsted, A.J., Brown, E.E., Campa, D., Vachon, C.M., Netea, M.G., Canzian, F., Försti, A., Sainz, J., Clavero, E., Sanchez-Maldonado, J.M., Macauda, A., Horst, R. ter, Sampaio-Marques, B., Jurczyszyn, A., Clay-Gilmour, A., Stein, A., Hildebrandt, M.A., Weinhold, N., Buda, G., García-Sanz, R., Tomczak, W., Vogel, U., Jerez, A., Zawirska, D., Wątek, M., Hofmann, J.N., Landi, S., Spinelli, J.J., Butrym, A., Kumar, A., Martínez-López, J., Galimberti, S., Sarasquete, M.E., Subocz, E., Iskierka-Jażdżewska, E., Giles, G.G., Rybicka-Ramos, M., Kruszewski, M., Abildgaard, N., Verdejo, F.G., Sánchez Rovira, P., Silva Filho, M.I. da, Kadar, K., Razny, M., Cozen, W., Pelosini, M., Jurado, M., Bhatti, P., Dudzinski, M., Druzd-Sitek, A., Orciuolo, E., Li, Y., Norman, A.D., Zaucha, J.M., Reis, R.M., Markiewicz, M., Rodríguez Sevilla, J.J., Andersen, V., Jamroziak, K., Hemminki, K., Berndt, S.I., Rajkumar, V., Mazur, G., Kumar, S.K., Ludovico, P., Nagler, A., Chanock, S.J., Dumontet, C., Machiela, M.J., Varkonyi, J., Camp, N.J., Ziv, E., Vangsted, A.J., Brown, E.E., Campa, D., Vachon, C.M., Netea, M.G., Canzian, F., Försti, A., and Sainz, J.

Abstract

Item does not contain fulltext, Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10(-9)) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10(-4)-5.79 × 10(-14)). Mechanistically, we found that the ULK4(rs6599175) SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10(-4)), whereas the IKBKE(rs17433804) SNP correlated with the number of transitional CD24(+)CD38(+) B cells (p = 4.8 × 10(-4)) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10(-4)). We also found that the CD46(rs1142469) SNP correlated with numbers of CD19(+) B cells, CD19(+)CD3(-) B cells, CD5(+)IgD(-) cells, IgM(-) cells, IgD(-)IgM(-) cells, and CD4(-)CD8(-) PBMCs (p = 4.9 × 10(-4)-8.6 × 10(-4)) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2A(rs2811710) SNP correlated with levels of CD4(+)EMCD45RO(+)CD27(-) cells (p = 9.3 × 10(-4)). These results s

Published
2023

3. Identification of novel genetic loci for risk of multiple myeloma by functional annotation.

Author

Macauda, A., Briem, K., Clay-Gilmour, A., Cozen, W., Försti, A., Giaccherini, M., Corradi, C., Sainz, J., Niazi, Y., Horst, R. ter, Li, Y., Netea, M.G., Vogel, U., Hemminki, K., Slager, S.L., Varkonyi, J., Andersen, V., Iskierka-Jazdzewska, E., Mártinez-Lopez, J., Zaucha, J., Camp, N.J., Rajkumar, S.V., Druzd-Sitek, A., Bhatti, P., Chanock, S.J., Kumar, S.K., Subocz, E., Mazur, G., Landi, S., Machiela, M.J., Jerez, A., Norman, A.D., Hildebrandt, M.A., Kadar, K., Berndt, S.I., Ziv, E., Buda, G., Nagler, A., Dumontet, C., Raźny, M., Watek, M., Butrym, A., Grzasko, N., Dudzinski, M., Rybicka-Ramos, M., Matera, E.L., García-Sanz, R., Goldschmidt, H., Jamroziak, K., Jurczyszyn, A., Clavero, E., Giles, G.G., Pelosini, M., Zawirska, D., Kruszewski, M., Marques, H., Haastrup, E., Sánchez-Maldonado, J.M., Bertsch, U., Rymko, M., Raab, M.S., Brown, E.E., Hofmann, J.N., Vachon, C., Campa, D., Canzian, F., Macauda, A., Briem, K., Clay-Gilmour, A., Cozen, W., Försti, A., Giaccherini, M., Corradi, C., Sainz, J., Niazi, Y., Horst, R. ter, Li, Y., Netea, M.G., Vogel, U., Hemminki, K., Slager, S.L., Varkonyi, J., Andersen, V., Iskierka-Jazdzewska, E., Mártinez-Lopez, J., Zaucha, J., Camp, N.J., Rajkumar, S.V., Druzd-Sitek, A., Bhatti, P., Chanock, S.J., Kumar, S.K., Subocz, E., Mazur, G., Landi, S., Machiela, M.J., Jerez, A., Norman, A.D., Hildebrandt, M.A., Kadar, K., Berndt, S.I., Ziv, E., Buda, G., Nagler, A., Dumontet, C., Raźny, M., Watek, M., Butrym, A., Grzasko, N., Dudzinski, M., Rybicka-Ramos, M., Matera, E.L., García-Sanz, R., Goldschmidt, H., Jamroziak, K., Jurczyszyn, A., Clavero, E., Giles, G.G., Pelosini, M., Zawirska, D., Kruszewski, M., Marques, H., Haastrup, E., Sánchez-Maldonado, J.M., Bertsch, U., Rymko, M., Raab, M.S., Brown, E.E., Hofmann, J.N., Vachon, C., Campa, D., and Canzian, F.

Abstract

Contains fulltext : 299996.pdf (Publisher’s version ) (Open Access), 01 november 2023

Published
2023

4. Changes in Stem Cell Transplant activity and procedures during SARS-CoV2 pandemic in Italy: an Italian Bone Marrow Transplant Group (GITMO) nationwide analysis (TransCOVID-19 Survey)

Author

Russo, D, Polverelli, N, Malagola, M, Farina, M, Leoni, A, Bernardi, S, Mammoliti, S, Sacchi, N, Martino, M, Ciceri, F, Zallio, F, Olivieri, A, Falcioni, S, Storti, G, Michieli, M, Carluccio, P, Grassi, A, Oldani, E, Bonifazi, F, Prete, A, Cavattoni, I, Maffeis, M, Pastore, D, Vacca, A, Caravelli, D, Mirabile, M, Mordini, N, Nozzoli, C, Faraci, M, Federico, V, Ronconi, S, Skert, C, Onida, F, Marcatti, M, Piemontese, S, Narni, F, Balduzzi, A, De Simone, G, Picardi, A, De Gobbi, M, Calore, E, Tringali, S, Zecca, M, Secondino, S, Guiducci, B, Pelosini, M, Zuffa, E, Facchini, L, Imola, M, Iori, A, Proia, A, Sica, S, Armiento, D, Carella, A, Dellacasa, C, Fagioli, F, Rabusin, M, Ferrario, A, Elice, F, Russo D., Polverelli N., Malagola M., Farina M., Leoni A., Bernardi S., Mammoliti S., Sacchi N., Martino M., Ciceri F., Zallio F., Olivieri A., Falcioni S., Storti G., Michieli M., Carluccio P., Grassi A., Oldani E., Bonifazi F., Prete A., Cavattoni I. M., Maffeis M., Pastore D., Vacca A., Caravelli D., Mirabile M., Mordini N., Nozzoli C., Faraci M., Federico V., Ronconi S., Skert C., Onida F., Marcatti M., Piemontese S., Narni F., Balduzzi A., De Simone G., Picardi A., De Gobbi M., Calore E., Tringali S., Zecca M., Secondino S., Guiducci B., Pelosini M., Zuffa E., Facchini L., Imola M., Iori A. P., Proia A., Sica S., Armiento D., Carella A. M., Dellacasa C. M., Fagioli F., Rabusin M., Ferrario A., Elice F., Russo, D, Polverelli, N, Malagola, M, Farina, M, Leoni, A, Bernardi, S, Mammoliti, S, Sacchi, N, Martino, M, Ciceri, F, Zallio, F, Olivieri, A, Falcioni, S, Storti, G, Michieli, M, Carluccio, P, Grassi, A, Oldani, E, Bonifazi, F, Prete, A, Cavattoni, I, Maffeis, M, Pastore, D, Vacca, A, Caravelli, D, Mirabile, M, Mordini, N, Nozzoli, C, Faraci, M, Federico, V, Ronconi, S, Skert, C, Onida, F, Marcatti, M, Piemontese, S, Narni, F, Balduzzi, A, De Simone, G, Picardi, A, De Gobbi, M, Calore, E, Tringali, S, Zecca, M, Secondino, S, Guiducci, B, Pelosini, M, Zuffa, E, Facchini, L, Imola, M, Iori, A, Proia, A, Sica, S, Armiento, D, Carella, A, Dellacasa, C, Fagioli, F, Rabusin, M, Ferrario, A, Elice, F, Russo D., Polverelli N., Malagola M., Farina M., Leoni A., Bernardi S., Mammoliti S., Sacchi N., Martino M., Ciceri F., Zallio F., Olivieri A., Falcioni S., Storti G., Michieli M., Carluccio P., Grassi A., Oldani E., Bonifazi F., Prete A., Cavattoni I. M., Maffeis M., Pastore D., Vacca A., Caravelli D., Mirabile M., Mordini N., Nozzoli C., Faraci M., Federico V., Ronconi S., Skert C., Onida F., Marcatti M., Piemontese S., Narni F., Balduzzi A., De Simone G., Picardi A., De Gobbi M., Calore E., Tringali S., Zecca M., Secondino S., Guiducci B., Pelosini M., Zuffa E., Facchini L., Imola M., Iori A. P., Proia A., Sica S., Armiento D., Carella A. M., Dellacasa C. M., Fagioli F., Rabusin M., Ferrario A., and Elice F.

Abstract

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.

Published
2021

5. Changes in Stem Cell Transplant activity and procedures during SARS-CoV2 pandemic in Italy: an Italian Bone Marrow Transplant Group (GITMO) nationwide analysis (TransCOVID-19 Survey)

Author

Russo D., Polverelli N., Malagola M., Farina M., Leoni A., Bernardi S., Mammoliti S., Sacchi N., Martino M., Ciceri F., Zallio F., Olivieri A., Falcioni S., Storti G., Michieli M., Carluccio P., Grassi A., Oldani E., Bonifazi F., Prete A., Cavattoni I. M., Maffeis M., Pastore D., Vacca A., Caravelli D., Mirabile M., Mordini N., Nozzoli C., Faraci M., Federico V., Ronconi S., Skert C., Onida F., Marcatti M., Piemontese S., Narni F., Balduzzi A., De Simone G., Picardi A., De Gobbi M., Calore E., Tringali S., Zecca M., Secondino S., Guiducci B., Pelosini M., Zuffa E., Facchini L., Imola M., Iori A. P., Proia A., Sica S., Armiento D., Carella A. M., Dellacasa C. M., Fagioli F., Rabusin M., Ferrario A., Elice F., Russo, D, Polverelli, N, Malagola, M, Farina, M, Leoni, A, Bernardi, S, Mammoliti, S, Sacchi, N, Martino, M, Ciceri, F, Zallio, F, Olivieri, A, Falcioni, S, Storti, G, Michieli, M, Carluccio, P, Grassi, A, Oldani, E, Bonifazi, F, Prete, A, Cavattoni, I, Maffeis, M, Pastore, D, Vacca, A, Caravelli, D, Mirabile, M, Mordini, N, Nozzoli, C, Faraci, M, Federico, V, Ronconi, S, Skert, C, Onida, F, Marcatti, M, Piemontese, S, Narni, F, Balduzzi, A, De Simone, G, Picardi, A, De Gobbi, M, Calore, E, Tringali, S, Zecca, M, Secondino, S, Guiducci, B, Pelosini, M, Zuffa, E, Facchini, L, Imola, M, Iori, A, Proia, A, Sica, S, Armiento, D, Carella, A, Dellacasa, C, Fagioli, F, Rabusin, M, Ferrario, A, Elice, F, Russo, D., Polverelli, N., Malagola, M., Farina, M., Leoni, A., Bernardi, S., Mammoliti, S., Sacchi, N., Martino, M., Ciceri, F., Zallio, F., Olivieri, A., Falcioni, S., Storti, G., Michieli, M., Carluccio, P., Grassi, A., Oldani, E., Bonifazi, F., Prete, A., Cavattoni, I. M., Maffeis, M., Pastore, D., Vacca, A., Caravelli, D., Mirabile, M., Mordini, N., Nozzoli, C., Faraci, M., Federico, V., Ronconi, S., Skert, C., Onida, F., Marcatti, M., Piemontese, S., Narni, F., Balduzzi, A., De Simone, G., Picardi, A., De Gobbi, M., Calore, E., Tringali, S., Zecca, M., Secondino, S., Guiducci, B., Pelosini, M., Zuffa, E., Facchini, L., Imola, M., Iori, A. P., Proia, A., Sica, S., Armiento, D., Carella, A. M., Dellacasa, C. M., Fagioli, F., Rabusin, M., Ferrario, A., and Elice, F.

Subjects
Homologous, Myeloid, medicine.medical_specialty, 2019-20 coronavirus outbreak, Bone marrow transplant, Coronavirus disease 2019 (COVID-19), Epidemiology, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hematopoietic stem cell transplantation, Acute, Humans, Italy, Pandemics, RNA, Viral, SARS-CoV-2, Stem Cell Transplantation, Transplantation, Homologous, COVID-19, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute, Article, hematopoietic stem cell transplantation, covid-19, pandemic, Internal medicine, Pandemic, medicine, Viral, Acute leukemia, Transplantation, Leukemia, business.industry, Hematology, Stem-cell research, RNA, Stem cell, business
Abstract

The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.

Published
2021

6. VENETOCLAX IN MULTI-RELAPSED MANTLE CELL LYMPHOMA PATIENTS: A REAL-LIFE MULTICENTRIC EXPERIENCE

Author

Galimberti, S, Marchi E, Pelosini, M, Benedetti, E, Urso, A, Cuneo, A, Musuraca, G, Martinelli, G, Quaglia, FM, Visco, C, Vallone, R, Muzi, C, Cairoli, R, Loseto, G, Guarini, A, Clerico, M, Ferrero, S, Petrini, M, Galimberti, S, Marchi, E, Pelosini, M, Benedetti, E, Urso, A, Cuneo, A, Musuraca, G, Martinelli, G, Quaglia, F, Visco, C, Vallone, R, Muzi, C, Cairoli, R, Loseto, G, Guarini, A, Clerico, M, Ferrero, S, and Petrini, M

Subjects
Hematology
Published
2021

8. Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party

Author

Bazarbachi, A.H., Hamed, R. Al, Labopin, M., Halaburda, K., Labussiere, H., Bernasconi, P., Schroyens, W., Gandemer, V., Schaap, N.P.M., Loschi, M., Jindra, P., Snowden, J., Wu, D., Guffroy, B., Rovira, M., Chantepie, S.P., Poiré, X., Lopez-Corral, L., Nikolousis, M., Pelosini, M., Ciceri, F., Baron, F., Bazarbachi, A., Corbacioglu, S., Savani, B.N., Peric, Z., Nagler, A., Carreras, E., Mohty, M., Bazarbachi, A.H., Hamed, R. Al, Labopin, M., Halaburda, K., Labussiere, H., Bernasconi, P., Schroyens, W., Gandemer, V., Schaap, N.P.M., Loschi, M., Jindra, P., Snowden, J., Wu, D., Guffroy, B., Rovira, M., Chantepie, S.P., Poiré, X., Lopez-Corral, L., Nikolousis, M., Pelosini, M., Ciceri, F., Baron, F., Bazarbachi, A., Corbacioglu, S., Savani, B.N., Peric, Z., Nagler, A., Carreras, E., and Mohty, M.

Abstract

Contains fulltext : 245127.pdf (Publisher’s version ) (Closed access), Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.

Published
2021

9. Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival

Author

Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., Gemignani, F., Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., and Gemignani, F.

Abstract

Contains fulltext : 232394.pdf (Publisher’s version ) (Closed access), We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

Published
2021

10. Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients.

Author

Vachon C.M., Canzian F., Campa D., Watek M., Jurczyszyn A., Brown E.E., Berndt S., Butrym A., Norman A.D., Gemignani F., Slager S.L., Macauda A., Piredda C., Clay-Gilmour A.I., Sainz J., Buda G., Markiewicz M., Barington T., Ziv E., Hildebrandt M.A.T., Belachew A.A., Varkonyi J., Prejzner W., Druzd-Sitek A., Spinelli J., Andersen N.F., Hofmann J.N., Dudzinski M., Martinez-Lopez J., Iskierka-Jazdzewska E., Milne R.L., Mazur G., Giles G.G., Ebbesen L.H., Rymko M., Jamroziak K., Subocz E., Reis R.M., Garcia-Sanz R., Suska A., Haastrup E.K., Zawirska D., Grzasko N., Vangsted A.J., Dumontet C., Kruszewski M., Dutka M., Camp N.J., Waller R.G., Tomczak W., Pelosini M., Razny M., Marques H., Abildgaard N., Vachon C.M., Canzian F., Campa D., Watek M., Jurczyszyn A., Brown E.E., Berndt S., Butrym A., Norman A.D., Gemignani F., Slager S.L., Macauda A., Piredda C., Clay-Gilmour A.I., Sainz J., Buda G., Markiewicz M., Barington T., Ziv E., Hildebrandt M.A.T., Belachew A.A., Varkonyi J., Prejzner W., Druzd-Sitek A., Spinelli J., Andersen N.F., Hofmann J.N., Dudzinski M., Martinez-Lopez J., Iskierka-Jazdzewska E., Milne R.L., Mazur G., Giles G.G., Ebbesen L.H., Rymko M., Jamroziak K., Subocz E., Reis R.M., Garcia-Sanz R., Suska A., Haastrup E.K., Zawirska D., Grzasko N., Vangsted A.J., Dumontet C., Kruszewski M., Dutka M., Camp N.J., Waller R.G., Tomczak W., Pelosini M., Razny M., Marques H., and Abildgaard N.

Abstract

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P <.05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P =.007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.Copyright © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.

Published
2021

11. Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients

Author

Macauda, A, Piredda, C, Clay-Gilmour, A, Sainz, J, Buda, G, Markiewicz, M, Barington, T, Ziv, E, Hildebrandt, MAT, Belachew, AA, Varkonyi, J, Prejzner, W, Druzd-Sitek, A, Spinelli, J, Andersen, NF, Hofmann, JN, Dudzinski, M, Martinez-Lopez, J, Iskierka-Jazdzewska, E, Milne, RL, Mazur, G, Giles, GG, Ebbesen, LH, Rymko, M, Jamroziak, K, Subocz, E, Reis, RM, Garcia-Sanz, R, Suska, A, Haastrup, EK, Zawirska, D, Grzasko, N, Vangsted, AJ, Dumontet, C, Kruszewski, M, Dutka, M, Camp, NJ, Waller, RG, Tomczak, W, Pelosini, M, Razny, M, Marques, H, Abildgaard, N, Watek, M, Jurczyszyn, A, Brown, EE, Berndt, S, Butrym, A, Vachon, CM, Norman, AD, Slager, SL, Gemignani, F, Canzian, F, Campa, D, Macauda, A, Piredda, C, Clay-Gilmour, A, Sainz, J, Buda, G, Markiewicz, M, Barington, T, Ziv, E, Hildebrandt, MAT, Belachew, AA, Varkonyi, J, Prejzner, W, Druzd-Sitek, A, Spinelli, J, Andersen, NF, Hofmann, JN, Dudzinski, M, Martinez-Lopez, J, Iskierka-Jazdzewska, E, Milne, RL, Mazur, G, Giles, GG, Ebbesen, LH, Rymko, M, Jamroziak, K, Subocz, E, Reis, RM, Garcia-Sanz, R, Suska, A, Haastrup, EK, Zawirska, D, Grzasko, N, Vangsted, AJ, Dumontet, C, Kruszewski, M, Dutka, M, Camp, NJ, Waller, RG, Tomczak, W, Pelosini, M, Razny, M, Marques, H, Abildgaard, N, Watek, M, Jurczyszyn, A, Brown, EE, Berndt, S, Butrym, A, Vachon, CM, Norman, AD, Slager, SL, Gemignani, F, Canzian, F, and Campa, D

Abstract

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.

Published
2021

16. Pancreatoduodenectomy for groove pancreatitis Report of two cases

Author

Fregoli, L., Matteo Palmeri, Napoli, L., Marco, S., Pelosini, M., Bertolucci, A., Galatioto, C., Cengeli, I., and Chiarugi, M.

Subjects
Diagnosis, Differential, Male, Pancreatic Neoplasms, Pancreatitis, Alcoholic, Recurrence, Pancreatitis, Chronic, Smoking, Humans, Middle Aged, Tomography, X-Ray Computed, Duodenoscopy, Magnetic Resonance Imaging, Pancreaticoduodenectomy
Abstract

Groove pancreatitis is a rare condition with patients having clinical characteristics similar to those of chronic pancreatitis. Differentiating on clinical and radiological basis between groove pancreatitis and paraduodenal head cancer can be extremely challenging. Due to diagnostic uncertainty and to poor response to medical treatment surgery may offer these patients the best chance of cure. As the main localization of the inflammatory process is at the groove between the duodenum and the head of the pancreas, pancreato-duodenectomy is proposed as the most reliable surgical procedure. We report about two patients presenting with clinical and radiological features suggesting a groove pancreatitis in which control of symptoms was achieved by pancreatoduodenectomy.Groove pancreatitis, Paraduodenal pancreatic cancer.La “groove pancreatitis” è una forma rara di pancreatite cronica interessante prevalentemente il solco duodenopancreatico. La sua diagnosi differenziale con i tumori maligni della testa del pancreas può essere estremamente difficile. In considerazione della incertezza diagnostica differenziale con i tumori della testa e della scarsa risposta alla terapia medica, la chirurgia può offrire il risultato terapeutico migliore. Poiché il processo infiammatorio coinvolge l’area duodeno-cefalopancreatica, l’intervento di pancreato-duodenectomia è proposto come migliore strategia chirurgica. Nel report sono presentati due casi di pazienti con quadro clinico-radiologico suggestivo di “groove pancreatitis” curati con successo mediante intervento di pancreato-duodenectomia con conservazione del piloro.

Published
2016

17. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

Author

Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., on behalf of the GIMEMA CML Working Party (Lucarelli, G., Polimeno, G., Ladetto, M., Pini, M., Rupoli, S., Scortechini, A. R., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Specchia, G., Russo, Rossi., Rambaldi, A., Ferrari, M. L., Palandri, F., Luatti, S., Iacobucci, I., Bochicchio, M. T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Giuliani, G., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Molica, S., Lentini, M., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cuneo, A., Ciccone, M., Bosi, A., Gozzini, A., Gobbi, M., Pierri, I., Chianese, R., De Blasio, A., Ciccone, F., Capochiani, E., Pelosini, M., Musolino, C., Russo, S., Cortelezzi, A., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti-Passerini, C., Luciano, L., Izzo, B., Ferrara, F., Annunziata, M., Mettivier, V., Sessa, U., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidor, I., Di Bartolomeo, P., Di Lorenzo, R., Vallisa, D., Trabacch, I., Pizzuti, M., Zuffa, E., Salvucci, M., Ronco, F., Lelo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Sica, S., Sorà, F., Latagliata, R., De Fabritiis, P., Trawiska, M., Amadori, S., Cantonetti, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Mengarelli, A., Romano, A., Tafuri, A., Montefusc, O., Iuliano, F., Infusino, S., Dore, F., Fozza, C., Bocchia, M., Defina, M., Liberati, Am., Luzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Nicolosi, M., Gottardi, M., Calistri, E., Fanin, R., Tiribelli, M., Pizzolo, G., Bonifacio, M., Rodeghiero, F., Di Bona, E. )., Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., and on behalf of the GIMEMA CML Working Party [, Palandri F.], Pane, Fabrizio, Gugliotta, G, Breccia, M, Stagno, F, Iurlo, A, Albano, F, Abruzzese, E, Martino, B, Levato, L, Intermesoli, T, Pregno, P, Rossi, G, Gherlinzoni, F, Leoni, P, Cavazzini, F, Venturi, C, Soverini, S, Testoni, N, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Baccarani, M, and GAMBACORTI PASSERINI, C

Subjects
DIAGNOSED CHRONIC-PHASE, Oncology, Male, Cancer Research, Time Factors, bcr-abl, Fusion Proteins, bcr-abl, Antineoplastic Agent, Hematology, Anesthesiology and Pain Medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Cumulative incidence, Young adult, Chronic, Aged, 80 and over, Leukemia, PATIENTS RECEIVING IMATINIB, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITORS, BCR-ABL1 TRANSCRIPT LEVELS, EARLY MOLECULAR RESPONSE, CML WORKING PARTY, 3-YEAR FOLLOW-UP, EUROPEAN LEUKEMIANET, 400 MG, Myeloid leukemia, Middle Aged, Prognosis, Treatment Outcome, Retreatment, Imatinib Mesylate, Female, Tyrosine kinase, Human, medicine.drug, Adult, medicine.medical_specialty, Time Factor, Adolescent, Prognosi, Protein Kinase Inhibitor, Socio-culturale, Antineoplastic Agents, Treatment results, Follow-Up Studie, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Fusion Proteins, Imatinib, Follow-Up Studies, Surgery, Imatinib mesylate, BCR-ABL Positive, business, Myelogenous
Abstract

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Published
2015

35. Allogeneic Hematopoietic Stem Cell Transplant (HSCT) for Patients in the 6th and 7th Decades of Life with AML or MDS Using Myeloablative, Reduced Toxicity IV Busulfan/Fludarabine (BuFlu) Conditioning Regimen

Author

Alatrash, G., primary, Andersson, B., additional, Pelosini, M., additional, Rondon, G., additional, Qazilbash, M., additional, Giralt, S., additional, de Padua Silva, L., additional, Hosing, C., additional, Kebriaei, P., additional, Zhang, W., additional, Saliba, R., additional, Champlin, R., additional, and de Lima, M., additional

Published
2009
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40. The Efficacy of Rituximab plus Hyper-CVAD Regimen in Mantle Cell Lymphoma Is Independent of FCγRIIIa and FCγRIIa Polymorphisms

Author

Galimberti, S., primary, Palumbo, G.A., additional, Caracciolo, F., additional, Benedetti, E., additional, Pelosini, M., additional, Brizzi, S., additional, Ciabatti, E., additional, Fazzi, R., additional, Stelitano, C., additional, Quintana, G., additional, Conte, E., additional, Tibullo, D., additional, Di Raimondo, F., additional, and Petrini, M., additional

Published
2007
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46. COMPARISON BETWEEN BEAM AND FEAM CONDITIONING REGIMEN IN PATIENTS AFFECTED BY LYMPHOMA SUBJECTED TO SELF TRANSPLANTATION OF HAEMATOPOIETIC STEM CELLS: A MULTI-CENTRIC RETROSPECTIVE STUDY OF THE ITALIAN FOUNDATION OF LYMPHOMAS (FIL)

Author

Olivieri, J., Mosna, F., Pelosini, M., Fama, A., Ferrero, S., Carli, G., Giannoccaro, M., Sgherza, N., Rattotti, S., Marino, D., Loseto, G., Mazzone, A. M., Calimeri, T., Maria Chiara Tisi, Tomei, G., Chiusolo, P., Perali, G., Billio, A., Orciuolo, E., Codeluppi, K., Stefani, P. M., Ghione, P., Gherlinzoni, F., Olivieri, A., Federici, I., Borghero, C., Centurioni, R., Matera, R., Finotto, S., Cascavilla, N., Fanin, R., and Zaja, F.

48. Prognostic value of expression quantitative trait loci in multiple myeloma prognosis

Author

Macauda, A., Piredda, C., Buda, G., Gemignani, F., Pelosini, M., Reis, R. M., Sainz, J., Tomczak, W., Zawirska, D., Rymko, M., Razny, M., Dudzinski, M., Druzd-Sitek, A., Garcia-Sanz, R., Watek, M., Subocz, E., Martinez Lopez, J., Prejzner, W., Krzysztof Jamroziak, Ebbesen, L. Hyldahl, Butrym, A., Dumontet, C., Abildgaard, N., Mazur, G., Suska, A., Varkonyi, J., Kruszewski, M., Vangsted, A. J., Markiewicz, M., Canzian, F., and Campa, D.

49. Identification of novel genetic loci for risk of multiple myeloma by functional annotation.

Author

Macauda A, Briem K, Clay-Gilmour A, Cozen W, Försti A, Giaccherini M, Corradi C, Sainz J, Niazi Y, Ter Horst R, Li Y, Netea MG, Vogel U, Hemminki K, Slager SL, Varkonyi J, Andersen V, Iskierka-Jazdzewska E, Mártinez-Lopez J, Zaucha J, Camp NJ, Rajkumar SV, Druzd-Sitek A, Bhatti P, Chanock SJ, Kumar SK, Subocz E, Mazur G, Landi S, Machiela MJ, Jerez A, Norman AD, Hildebrandt MAT, Kadar K, Berndt SI, Ziv E, Buda G, Nagler A, Dumontet C, Raźny M, Watek M, Butrym A, Grzasko N, Dudzinski M, Rybicka-Ramos M, Matera EL, García-Sanz R, Goldschmidt H, Jamroziak K, Jurczyszyn A, Clavero E, Giles GG, Pelosini M, Zawirska D, Kruszewski M, Marques H, Haastrup E, Sánchez-Maldonado JM, Bertsch U, Rymko M, Raab MS, Brown EE, Hofmann JN, Vachon C, Campa D, and Canzian F

Subjects
Humans, Genetic Loci, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Multiple Myeloma genetics
Published
2023
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50. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Author

Clavero E, Sanchez-Maldonado JM, Macauda A, Ter Horst R, Sampaio-Marques B, Jurczyszyn A, Clay-Gilmour A, Stein A, Hildebrandt MAT, Weinhold N, Buda G, García-Sanz R, Tomczak W, Vogel U, Jerez A, Zawirska D, Wątek M, Hofmann JN, Landi S, Spinelli JJ, Butrym A, Kumar A, Martínez-López J, Galimberti S, Sarasquete ME, Subocz E, Iskierka-Jażdżewska E, Giles GG, Rybicka-Ramos M, Kruszewski M, Abildgaard N, Verdejo FG, Sánchez Rovira P, da Silva Filho MI, Kadar K, Razny M, Cozen W, Pelosini M, Jurado M, Bhatti P, Dudzinski M, Druzd-Sitek A, Orciuolo E, Li Y, Norman AD, Zaucha JM, Reis RM, Markiewicz M, Rodríguez Sevilla JJ, Andersen V, Jamroziak K, Hemminki K, Berndt SI, Rajkumar V, Mazur G, Kumar SK, Ludovico P, Nagler A, Chanock SJ, Dumontet C, Machiela MJ, Varkonyi J, Camp NJ, Ziv E, Vangsted AJ, Brown EE, Campa D, Vachon CM, Netea MG, Canzian F, Försti A, and Sainz J

Subjects
Humans, Leukocytes, Mononuclear pathology, Biomarkers, Immunoglobulin M, Autophagy, Multiple Myeloma genetics, Multiple Myeloma pathology
Abstract

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10 -9 ) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46 , IKBKE , PARK2 , ULK4 , ATG5 , and CDKN2A associated with MM risk ( p = 4.47 × 10 -4 -5.79 × 10 -14 ). Mechanistically, we found that the ULK4 rs6599175 SNP correlated with circulating concentrations of vitamin D3 ( p = 4.0 × 10 -4 ), whereas the IKBKE rs17433804 SNP correlated with the number of transitional CD24 + CD38 + B cells ( p = 4.8 × 10 -4 ) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 ( p = 3.6 × 10 -4 ). We also found that the CD46 rs1142469 SNP correlated with numbers of CD19 + B cells, CD19 + CD3 - B cells, CD5 + IgD - cells, IgM - cells, IgD - IgM - cells, and CD4 - CD8 - PBMCs ( p = 4.9 × 10 -4 -8.6 × 10 -4 ) and circulating concentrations of interleukin (IL)-20 ( p = 0.00082). Finally, we observed that the CDKN2A rs2811710 SNP correlated with levels of CD4 + EMCD45RO + CD27 - cells ( p = 9.3 × 10 -4 ). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3 - , MCP-2 - , and IL20-dependent pathways.

Published
2023
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