Определение статуса метилирования промоторных областей генов MARCH11, HOXA9, PTGDR и UNCX у пациентов с немелкоклеточным раком легкого

The aim of this study was to determine the methylation status of the promoter regions of MARCH11, HOXA9, PTGDR, and UNCX genes in the tumor and non-tumor lung tissue in patients with non-small cell lung cancer (NSCLC). A relative level of methylation of the promoter regions of MARCH11, HOXA9, PTGDR, and UNCX genes was determined by the quantitative methylation-specific PCR in 73 patients with NSCLC. The quantitative methylation-specific reaction was performed both for tumor tissue samples and non-tumor tissue samples of the same patient. For each of the samples, a reaction was set both by the investigated genes (MARCH11, UNCX, HOXA9, and PTGDR) and by the reference beta-actin gene (β-actin). Positive levels of methylation of the HOXA9 gene were established for 83.5 % patients; the MARCH11 gene – for 80.8 % patients; the PTGDR gene – for 68.4 % patients; the UNCX gene – for 84.9 % patients. In the study group of patients with NSCLC, significant differences were found in the relative levels of methylation of the promoter regions of MARCH11, HOXA9, PTGDR, and UNCX genes in the tumor and non-tumor lung tissue. The data suggest that hypermethylation of MARCH11, HOXA9, PTGDR, and UNCX genes may play a role in NSCLC tumor progression.Целью данного исследования было определение статуса метилирования промоторных областей генов MARCH11, HOXA9, PTGDR и UNCX в опухолевой и неопухолевой ткани легкого у пациентов с немелкоклеточным раком легкого (НМРЛ). Относительный уровень метилирования промоторных областей генов MARCH11, HOXA9, PTGDR, UNCX определяли методом количественной метилспецифической ПЦР у 73 пациентов с НМРЛ. Количественная метилспецифическая реакция проводилась как для образцов опухолевой ткани, так и для образцов неопухолевой ткани одного и того же пациента. Для каждого из образцов ставили реакцию по изучаемым генам (MARCH11, UNCX, HOXA9, PTGDR) и по референсному гену бета-актина (β-actin). Установлены положительные уровни метилирования гена HOXA9 у 83,5 % пациентов, гена MARCH11 – у 80,8 % пациентов, гена PTGDR – у 68,4 % пациентов, гена UNCX – у 84,9 % пациентов. В исследуемой группе пациентов с НМРЛ выявлены достоверные различия относительных уровней метилирования промоторных регионов генов MARCH11, HOXA9, PTGDR и UNCX в опухолевой и неопухолевой ткани легкого. Эти данные позволяют предположить, что гиперметилирование генов MARCH11, HOXA9, PTGDR и UNCX может играть роль в опухолевой прогрессии НМРЛ

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

GENETIC POLYMORPHISMS OF VEGF AND THEIR INFLUENCE ON THE DEVELOPMENT AND PROGNOSIS OF NON-SMALL CELL LUNG CANCER

Lung cancer is the most common malignant tumor in the world associated with high mortality. One of the principle positions in the progression of the neoplasm and spread of the disease belongs to processes related to angiogenesis. Aim of the study: to present effects of the rs699947, rs2010963 and rs3025039 polymorphisms of the VEGF gene responsible for angiogenesis on the extent of tumor progression and survival in patients with non-small cell lung cancer (NSCLC). Material and methods. A total of 172 patients with a diagnosis of NSCLC were included in the study group. All cases were classified according to the TNM / pTNM (7th edition, 2011). The patients were genotyped for the selected polymorphic loci by PCR. Survival analysis of was performed using the life tables in intervals and the Kaplan-Meier method. The results of the study indicate that genetic polymorphism of VEGF influences the course and prognosis of NSCLC. Conclusions: – homozygous genotype -2578CC of the VEGF gene is associated with a greater degree of spread of the tumor; – differences in survival appear after 6 months of the surgery; – survival rate of patients with the VEGF -2578AA genotype during the first years of life exceeds the number of individuals with the VEGF -2578CC genotype; – heterozygous variant of the VEGF -2578CA gene was significantly more common in patients free from disease

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

195sinoneBackground: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value &lt; 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.nonePagano L.; Salmanton-Garcia J.; Marchesi F.; Busca A.; Corradini P.; Hoenigl M.; Klimko N.; Koehler P.; Pagliuca A.; Passamonti F.; Verga L.; Visek B.; Ilhan O.; Nadali G.; Weinbergerova B.; Cordoba-Mascunano R.; Marchetti M.; Collins G.P.; Farina F.; Cattaneo C.; Cabirta A.; Gomes-Silva M.; Itri F.; van Doesum J.; Ledoux M.-P.; Cernan M.; Jaksic O.; Duarte R.F.; Magliano G.; Omrani A.S.; Fracchiolla N.S.; Kulasekararaj A.; Valkovic T.; Poulsen C.B.; Machado M.; Glenthoj A.; Stoma I.; Racil Z.; Piukovics K.; Navratil M.; Emarah Z.; Sili U.; Maertens J.; Blennow O.; Bergantim R.; Garcia-Vidal C.; Prezioso L.; Guidetti A.; del Principe M.I.; Popova M.; de Jonge N.; Ormazabal-Velez I.; Fernandez N.; Falces-Romero I.; Cuccaro A.; Meers S.; Buquicchio C.; Antic D.; Al-Khabori M.; Garcia-Sanz R.; Biernat M.M.; Tisi M.C.; Sal E.; Rahimli L.; Colovic N.; Schonlein M.; Calbacho M.; Tascini C.; Miranda-Castillo C.; Khanna N.; Mendez G.-A.; Petzer V.; Novak J.; Besson C.; Dulery R.; Lamure S.; Nucci M.; Zambrotta G.; Zak P.; Seval G.C.; Bonuomo V.; Mayer J.; Lopez-Garcia A.; Sacchi M.V.; Booth S.; Ciceri F.; Oberti M.; Salvini M.; Izuzquiza M.; Nunes-Rodrigues R.; Ammatuna E.; Obr A.; Herbrecht R.; Nunez-Martin-Buitrago L.; Mancini V.; Shwaylia H.; Sciume M.; Essame J.; Nygaard M.; Batinic J.; Gonzaga Y.; Regalado-Artamendi I.; Karlsson L.K.; Shapetska M.; Hanakova M.; El-Ashwah S.; Borbenyi Z.; Colak G.M.; Nordlander A.; Dragonetti G.; Maraglino A.M.E.; Rinaldi A.; De Ramon-Sanchez C.; Cornely O.A.; Finizio O.; Fazzi R.; Sapienza G.; Chauchet A.; Van Praet J.; Prattes J.; Dargenio M.; Rossi C.; Shirinova A.; Malak S.; Tafuri A.; Ommen H.-B.; Bologna S.; Khedr R.A.; Choquet S.; Joly B.; Ceesay M.M.; Philippe L.; Kho C.S.; Desole M.; Tsirigotis P.; Otasevic V.; Borducchi D.M.M.; Antoniadou A.; Gaziev J.; Almaslamani M.A.; Garcia-Pouton N.; Paterno G.; Torres-Lopez A.; Tarantini G.; Mellinghoff S.; Grafe S.; Borschel N.; Passweg J.; Merelli M.; Barac A.; Wolf D.; Shaikh M.U.; Thieblemont C.; Bernard S.; Funke V.A.M.; Daguindau E.; Khostelidi S.; Nucci F.M.; Martin-Gonzalez J.-A.; Landau M.; Soussain C.; Laureana C.; Lacombe K.; Kohn M.; Aliyeva G.; Piedimonte M.; Fouquet G.; Rego M.; Hoell-Neugebauer B.; Cartron G.; Pinto F.; Alburquerque A.M.; Passos J.; Yilmaz A.F.; Redondo-Izal A.-M.; Altuntas F.; Heath C.; Kolditz M.; Schalk E.; Guolo F.; Karthaus M.; Della Pepa R.; Vinh D.; Noel N.; Deau Fischer B.; Drenou B.; Mitra M.E.; Meletiadis J.; Bilgin Y.M.; Jindra P.; Espigado I.; Drgona L.; Serris A.; Di Blasi R.; Ali N.Pagano, L.; Salmanton-Garcia, J.; Marchesi, F.; Busca, A.; Corradini, P.; Hoenigl, M.; Klimko, N.; Koehler, P.; Pagliuca, A.; Passamonti, F.; Verga, L.; Visek, B.; Ilhan, O.; Nadali, G.; Weinbergerova, B.; Cordoba-Mascunano, R.; Marchetti, M.; Collins, G. P.; Farina, F.; Cattaneo, C.; Cabirta, A.; Gomes-Silva, M.; Itri, F.; van Doesum, J.; Ledoux, M. -P.; Cernan, M.; Jaksic, O.; Duarte, R. F.; Magliano, G.; Omrani, A. S.; Fracchiolla, N. S.; Kulasekararaj, A.; Valkovic, T.; Poulsen, C. B.; Machado, M.; Glenthoj, A.; Stoma, I.; Racil, Z.; Piukovics, K.; Navratil, M.; Emarah, Z.; Sili, U.; Maertens, J.; Blennow, O.; Bergantim, R.; Garcia-Vidal, C.; Prezioso, L.; Guidetti, A.; del Principe, M. I.; Popova, M.; de Jonge, N.; Ormazabal-Velez, I.; Fernandez, N.; Falces-Romero, I.; Cuccaro, A.; Meers, S.; Buquicchio, C.; Antic, D.; Al-Khabori, M.; Garcia-Sanz, R.; Biernat, M. M.; Tisi, M. C.; Sal, E.; Rahimli, L.; Colovic, N.; Schonlein, M.; Calbacho, M.; Tascini, C.; Miranda-Castillo, C.; Khanna, N.; Mendez, G. -A.; Petzer, V.; Novak, J.; Besson, C.; Dulery, R.; Lamure, S.; Nucci, M.; Zambrotta, G.; Zak, P.; Seval, G. C.; Bonuomo, V.; Mayer, J.; Lopez-Garcia, A.; Sacchi, M. V.; Booth, S.; Ciceri, F.; Oberti, M.; Salvini, M.; Izuzquiza, M.; Nunes-Rodrigues, R.; Ammatuna, E.; Obr, A.; Herbrecht, R.; Nunez-Martin-Buitrago, L.; Mancini, V.; Shwaylia, H.; Sciume, M.; Essame, J.; Nygaard, M.; Batinic, J.; Gonzaga, Y.; Regalado-Artamendi, I.; Karlsson, L. K.; Shapetska, M.; Hanakova, M.; El-Ashwah, S.; Borbenyi, Z.; Colak, G. M.; Nordlander, A.; Dragonetti, G.; Maraglino, A. M. E.; Rinaldi, A.; De Ramon-Sanchez, C.; Cornely, O. A.; Finizio, O.; Fazzi, R.; Sapienza, G.; Chauchet, A.; Van Praet, J.; Prattes, J.; Dargenio, M.; Rossi, C.; Shirinova, A.; Malak, S.; Tafuri, A.; Ommen, H. -B.; Bologna, S.; Khedr, R. A.; Choquet, S.; Joly, B.; Ceesay, M. M.; Philippe, L.; Kho, C. S.; Desole, M.; Tsirigotis, P.; Otasevic, V.; Borducchi, D. M. M.; Antoniadou, A.; Gaziev, J.; Almaslamani, M. A.; Garcia-Pouton, N.; Paterno, G.; Torres-Lopez, A.; Tarantini, G.; Mellinghoff, S.; Grafe, S.; Borschel, N.; Passweg, J.; Merelli, M.; Barac, A.; Wolf, D.; Shaikh, M. U.; Thieblemont, C.; Bernard, S.; Funke, V. A. M.; Daguindau, E.; Khostelidi, S.; Nucci, F. M.; Martin-Gonzalez, J. -A.; Landau, M.; Soussain, C.; Laureana, C.; Lacombe, K.; Kohn, M.; Aliyeva, G.; Piedimonte, M.; Fouquet, G.; Rego, M.; Hoell-Neugebauer, B.; Cartron, G.; Pinto, F.; Alburquerque, A. M.; Passos, J.; Yilmaz, A. F.; Redondo-Izal, A. -M.; Altuntas, F.; Heath, C.; Kolditz, M.; Schalk, E.; Guolo, F.; Karthaus, M.; Della Pepa, R.; Vinh, D.; Noel, N.; Deau Fischer, B.; Drenou, B.; Mitra, M. E.; Meletiadis, J.; Bilgin, Y. M.; Jindra, P.; Espigado, I.; Drgona, L.; Serris, A.; Di Blasi, R.; Ali, N

COVID-19 infection in adult patients with hematological malignancies : a European Hematology Association Survey (EPICOVIDEHA)

Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientifc Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confrmed COVID19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non- Hodgkin lymphoma n=1084, myeloma n=684 and chronic lymphoid leukemia n=474) and myeloproliferative malignancies (mainly acute myeloid leukemia n=497 and myelodysplastic syndromes n=279). Severe/critical COVID-19 was observed in 63.8% of patients (n=2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate signifcantly decreased between the frst COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value<0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confrms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases