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1. 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

2. 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

3. 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

4. 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

5. Real life outcomes of patients aged >= 75 years old with acute promyelocytic leukemia: experience of the PETHEMA registry

Author

Salamero O, Mart?nez-Cuadr?n D, Sobas M, Benavente C, Vives S, De la Serna J, P?rez-Encinas M, Escoda L, Gil C, Brunet S, Ramos F, Esteve J, Amigo M, Krsnik I, Manso F, Arias J, Gonz?lez-Campos J, Serrano J, Oleksiuk J, Barrios M, Garc?a-Boyero R, Novo A, Sanz M, Montesinos P, Helbig G, Holowiecka A, Armatys A, Hawrylecka D, Golos A, Ejduk A, Majcherek M, Skret A, Czyzewska J, Grosicki S, Zarzycka E, Watek M, Piatkowska-Jakubas B, Holojda J, Pluta A, Podhorecka M, Gromek T, Guzicka E, Charlinski G, Paluszewska M, de Heredia J, Hern?ndez J, Rom?n A, de la Serna J, Negri S, Ray?n C, Fern?ndez-Calvo F, D?az-Mediavilla J, Tormo M, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garc?a R, Alcal? A, L?pez J, Rubio V, Linares M, Ribera J, San Miguel J, Deb?n G, de la C?mara R, Molines A, Loureiro C, Allegue M, Amador L, Mart? J, Madero L, Lassaletta A, Cabezudo M, Garc?a-Larana J, Rojas R, Ortega F, Pe?arrubia M, Puente F, Lopez-Ibor B, Bergua J, Ib??ez J, S?nchez P, Font L, Guinea J, Montero A, Gonz?lez M, Mart?n G, Mart?nez J, Verdeguer A, Garc?a P, Conde E, Garc?a J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonz?lez J, P?rez I, Molina J, Mateos M, Ardaiz M, Rodr?guez-Calvillo M, Poder?s C, Arn?n M, Duarte R, D?az-Morfa M, Mart?n-Chac?n E, Calvo-Villas J, Garc?a-Belmonte D, Hern?ndez-Maraver D, Miskiewicz W, PETHEMA Grp, and PALG Grp

Subjects
induction mortality in APL, APL real life outcomes, Elderly APL, APL prognostic factors, neoplasms
Abstract

Acute promyelocytic leukemia is infrequent among patients aged >= 75 years old, a population that is rarely eligible for clinical protocols. This study aims to analyze the treatment strategies and clinical outcomes of very old APL patients reported to the international PETHEMA registry. Between 1997 and 2017, among 2501 APL cases registered 120 were >= 75 years old. Treatment approaches were: AIDA regimen, 79 patients; ATRA alone, 23; 16, supportive care (SC) and 2, other strategies. Patients treated with AIDA were younger, had better ECOG and lower leukocytes. Complete remission (CR) was achieved in 65% of AIDA-group vs. 45% in the ATRA-group, being infections followed by bleeding the most frequent causes of induction death. Patients in CR after AIDA showed 3-year DFS of 73%. Our real-life series of very old APL patients provides a reference basis for future treatment strategies aiming to improve clinical outcomes in this challenging population.

Published
2019

6. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas M, Montesinos P, Boluda B, Bernal T, Vellenga E, Nomdedeu J, Gonzalez-Campos J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil-Cortes C, Tormo M, Salamero O, Manso F, Fernandez I, de la Serna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Escoda L, Lowenberg B, Sanz M, de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Gil C, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, San Miguel J, Coruna A, Deben G, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Brunet S, Ibanez J, Sanchez P, Novo A, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, van Marwijk M, de Lisa E, Golos A, Ejduk A, Armatys A, Zarzycka E, Knopinska W, Miskiewicz W, Jastrzab B, Pluta A, Paluszewska M, Podhorecka M, Gromek T, Jakubas B, Majcherek M, Skret A, Watek M, Charlinski G, Calbecka M, Becht R, Gadomska A, Rzenno E, Piszcz J, Grosicki S, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, PETHEMA Cooperative Grp, HOVON Cooperative Grp, PALG Cooperative Grp, and GATLA Cooperative Grp

Subjects
relapse, Acute promyelocytic leukemia, CD56, ATRA, chemotherapy, prognostic
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Published
2019

7. Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy

Author

Labrador J, Luno E, Vellenga E, Brunet S, Gonzalez-Campose J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil C, Tormo M, Salamero O, Manso F, Fernandez I, de laSerna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Cervera J, Calasanz M, Boluda B, Sobas M, Lowenberg B, Sanz M, Montesinos P, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Prates M, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, Holowiecka-Goral A, Jakubas B, Skret-Norwicz A, Bizgalska-Skrzypek P, Pluta A, Becht R, Kielbinski M, Watek M, Paluszewska M, Gadomska A, Rzenno E, Piszcz J, Ejduk A, Dobrzanska J, Calbecka M, Kostyra A, Malek M, Grosicki S, Knopinska W, Beltran de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, de la Serna J, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, Gonzalez San Miguel J, Deben G, Escoda L, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Ibanez J, Sanchez P, Novo A, Font L, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, Kooy M, de Lisa E, PETHEMA Grp, HOVON Grp, PALG Grp, and GATLA Grp

Subjects
relapse, complex karyotype, Acute promyelocytic leukemia, ATRA, chemotherapy, prognostic
Abstract

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

Published
2019

8. Zachorowalność i chorobowość na zespoły mielodysplastyczne w Polsce na podstawie badania rejestrowego OPINIA

Author

Drozd-Sokołowska, J., primary, Mądry, K., additional, Waszczuk-Gajda, A., additional, Sikorska, A., additional, Wajs, J., additional, Semeńczuk, G., additional, Szmigielska-Kapłon, A., additional, Zalewska, M., additional, Wasilewska, E., additional, Szwedyk, P., additional, Hołojda, J., additional, Watek, M., additional, Stella-Hołowiecka, B., additional, Soroka-Wojtaszko, M., additional, Homenda, W., additional, Polak, M., additional, Guzicka-Kazimierska, R., additional, Porowska, A., additional, and Dwilewicz-Trojaczek, J., additional

Published
2015
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9. Charakterystyka chorych na zespoły mielodysplastyczne na podstawie ogólnopolskiego prospektywnego rejestru MDS

Author

Dwilewicz-Trojaczek, J., primary, Mądry, K., additional, Waszczuk-Gajda, A., additional, Drozd-Sokołowska, J., additional, Stella-Hołowiecka, B., additional, Jachalska, A., additional, Szwedyk, P., additional, Kołkowska-Leśniak, A., additional, Sikorska, A., additional, Obara, A., additional, Watek, M., additional, Szczepańska, M., additional, Szmigielska-Kapłon, A., additional, Mendrek, W., additional, Kopińska, A., additional, Krochmalczyk, D., additional, Zawirska, D., additional, Subocz, E., additional, Guzicka-Kazimierska, R., additional, Masternak, A., additional, Kopacz, A., additional, Blajer-Olszewska, B., additional, Biedroń, M., additional, Hołojda, J., additional, Wasilewska, E., additional, Wojciechowska, M., additional, Urbanowicz, A., additional, Soroka-Wojtaszko, M., additional, Sokołowska, B., additional, Brzozowska-Marek, A., additional, and Jędrzejczak, W.W., additional

Published
2015
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11. Randomized Comparison of Cladribine Single (C) or in Combination with Cyclophosphamide (CC), and COP in Previously Untreated Low Grade B-Cell Non-Hodgkin Lymphoma Patients.

Author

Kalinka, E., primary, Wajs, J., additional, Sulek, K.S., additional, Blasinska-Morawiec, M., additional, Centkowski, P., additional, Ceglarek, B., additional, Robak, T., additional, Holowiecki, J., additional, Mazur, G., additional, Federowicz, I., additional, Jedrzejczak, W., additional, Watek, M., additional, and Warzocha, K., additional

Published
2006
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15. 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.

16. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients

Author

Paige M. Bracci, Celine M. Vachon, Thomas Martin, Shaji Kumar, Daniel J. Serie, Alexandra J. Greenberg, Laura Fejerman, Djordje Atanackovic, Brandt Jones, Federico Canzian, Robert B. Diasio, Vincent Rajkumar, Jeffrey L. Wolf, Blake T. Aftab, Alessandro Martino, Susan L. Slager, Herlander Marques, Donglei Hu, Eric Dean, Marek Dudziński, Martha Glenn, Yi Zhao, Marzena Wątek, Nicola J. Camp, Elad Ziv, Karen Curtin, Adam M. Lee, Juan Sainz, Joaquin Martinez-Lopez, Artur Jurczyszyn, Lisa A. Cannon-Albright, Charles Dumontet, Scott Huntsman, Jennifer L. Caswell-Jin, Annette Juul Vangsted, Daniele Campa, Gabriele Buda, Krzysztof Jamroziak, [Ziv,E, Hu,D, Caswell.Jin,J,H, Fejerman,L, Huntsman,S] Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Dean,E] Sutter Medical Center of Santa Rosa, Santa Rosa, California USA. [Martino,A, Campa,D, Canzian,F] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Serie,D] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida USA. [Curtin,K, Zhao,Y, Atanackovic,D, Glenn,M, Cannon-Albright,L, Jones,B, Camp,NJ] Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA. [Aftalb,B, Martin,T, Wolf,J]Division of Hematology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Bracci,P] Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California , USA. [Buda,G] Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital, Pisa, Italy. [Diasio,R, Lee,A] Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, Minnesota USA. [Dumontet,C] INSERM UMR 1052/CNRS 5286, Laboratoire de Cytologie Analytique, Faculte´ de Me´decine Rockefeller, Universite´ Claude Bernard Lyon I, Lyon, France. [Dudzinski,M] Department of Hematology, Rzeszow Regional Hospital, Rzeszow 35-301, Poland. [Greenberg,A] Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905, USA. [Greenberg,A, Vachon, C] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [Jamroziak,K] Department of Hematology, Medical University of Lodz, Lodz, Poland. [Jurczyszyn,A] Department of Hematology, Cracow University Hospital, Cracow, Poland. [Kumar,S, Rajkumar,V] Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. [Marques,H] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga , Portugal. [Martinez-Lopez,J] Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain. [Sainz,J] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. Department of Hematology, Virgen de las Nieves University Hospital, Granada, Spain. [Vangsted,AJ] Department of Hematology, Righospitalet and Roskilde Hospital, Copenhagen University, Copenhagen, Denmark. [Watek,M] Department of Hematology, Holycross Cancer Center, Kielce, Poland. [Slager,S] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota USA., and This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334). DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336 and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah.

Subjects
Oncology, medicine.medical_specialty, tumor, Ciências da Saúde [Ciências Médicas], General Physics and Astronomy, Genome-wide association study, Single-nucleotide polymorphism, Kaplan-Meier Estimate, Biology, Bioinformatics, Polymorphism, Single Nucleotide, survival, Article, General Biochemistry, Genetics and Molecular Biology, gene expression, genome, health risk, meta-analysis, polymorphism, social theory, Internal medicine, medicine, Humans, Allele, Gene, Multiple myeloma, Science & Technology, Multidisciplinary, General Chemistry, medicine.disease, Minor allele frequency, Meta-analysis, Cohort, Multiple Myeloma, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract

A corrigendum to this article was published on 09 December 2015: https://doi.org/10.1038/ncomms10203. The corrigendum is also available at: http://hdl.handle.net/1822/62281 This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334).DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCICancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah. In Utah, we thank Jathine Wong for support in formatting files and advice on R programming. Several authors (E.Z., N.C., F.C., C.V.) are members of the International Multiple Myeloma Consortium. We are grateful to the leadership and other members of the International Multiple Myeloma Consortium for facilitating this collaborative study.

Published
2015

17. 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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18. A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.

Author

Dicanio M, Giaccherini M, Clay-Gilmour A, Macauda A, Sainz J, Machiela MJ, Rybicka-Ramos M, Norman AD, Tyczyńska A, Chanock SJ, Barington T, Kumar SK, Bhatti P, Cozen W, Brown EE, Suska A, Haastrup EK, Orlowski RZ, Dudziński M, Garcia-Sanz R, Kruszewski M, Martinez-Lopez J, Beider K, Iskierka-Jazdzewska E, Pelosini M, Berndt SI, Raźny M, Jamroziak K, Rajkumar SV, Jurczyszyn A, Vangsted AJ, Collado PG, Vogel U, Hofmann JN, Petrini M, Butrym A, Slager SL, Ziv E, Subocz E, Giles GG, Andersen NF, Mazur G, Watek M, Lesueur F, Hildebrandt MAT, Zawirska D, Ebbesen LH, Marques H, Gemignani F, Dumontet C, Várkonyi J, Buda G, Nagler A, Druzd-Sitek A, Wu X, Kadar K, Camp NJ, Grzasko N, Waller RG, Vachon C, Canzian F, and Campa D

Subjects
Humans, Oncogenes, Alleles, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Predisposition to Disease, HSP40 Heat-Shock Proteins genetics, DNA-Binding Proteins genetics, RNA-Binding Proteins, Multiple Myeloma epidemiology, Multiple Myeloma genetics
Abstract

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10 -8 ) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10 -7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2023
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19. Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Author

Macauda A, Clay-Gilmour A, Hielscher T, Hildebrandt MAT, Kruszewski M, Orlowski RZ, Kumar SK, Ziv E, Orciuolo E, Brown EE, Försti A, Waller RG, Machiela MJ, Chanock SJ, Camp NJ, Rymko M, Raźny M, Cozen W, Várkonyi J, Piredda C, Pelosini M, Belachew AA, Subocz E, Hemminki K, Rybicka-Ramos M, Giles GG, Milne RL, Hofmann JN, Zaucha JM, Vangsted AJ, Goldschmidt H, Rajkumar SV, Tomczak W, Sainz J, Butrym A, Watek M, Iskierka-Jazdzewska E, Buda G, Robinson DP, Jurczyszyn A, Dudziński M, Martinez-Lopez J, Sinnwell JP, Slager SL, Jamroziak K, Reis RMV, Weinhold N, Bhatti P, Carvajal-Carmona LG, Zawirska D, Norman AD, Mazur G, Berndt SI, Campa D, Vachon CM, and Canzian F

Subjects
Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Genome-Wide Association Study methods, Multiple Myeloma genetics
Abstract

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival., Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed., Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P &lt; 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant., Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS., Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma., (©2022 American Association for Cancer Research.)

Published
2022
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20. 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 MS, Maccari G, Ter Horst R, Netea MG, Li Y, Grząśko N, Moreno V, Jurczyszyn A, Jerez A, Watek M, Varkonyi J, Garcia-Sanz R, Kruszewski M, Dudziński M, Kadar K, Jacobsen SEH, Mazur G, Andersen V, Rybicka M, Zawirska D, Raźny M, Zaucha JM, Ostrovsky O, Iskierka-Jazdzewska E, Reis RM, Stępień A, Beider K, Nagler A, Druzd-Sitek A, Marques H, Martìnez-Lopez J, Lesueur F, Avet-Loiseau H, Vangsted AJ, Krawczyk-Kulis M, Butrym A, Jamroziak K, Dumontet C, Vogel U, Rymko M, Pelosini M, Subocz E, Szombath G, Sarasquete ME, Silvestri R, Morani F, Landi S, Campa D, Canzian F, and Gemignani F

Subjects
Adult, Aged, Case-Control Studies, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genotype, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Polymorphism, Single Nucleotide, RNA, Messenger genetics, RNA, Messenger metabolism, Risk Factors, Survival Analysis, 3' Untranslated Regions genetics, Genetic Predisposition to Disease genetics, Germ-Line Mutation, Multiple Myeloma genetics
Abstract

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., (© 2020 Union for International Cancer Control.)

Published
2021
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21. Genetically determined telomere length and multiple myeloma risk and outcome.

Author

Giaccherini M, Macauda A, Orciuolo E, Rymko M, Gruenpeter K, Dumontet C, Raźny M, Moreno V, Buda G, Beider K, Varkonyi J, Avet-Loiseau H, Martinez-Lopez J, Marques H, Watek M, Sarasquete ME, Andersen V, Karlin L, Suska A, Kruszewski M, Abildgaard N, Dudziński M, Butrym A, Nagler A, Vangsted AJ, Kadar K, Waldemar T, Jamroziak K, Jacobsen SEH, Ebbesen LH, Taszner M, Mazur G, Lesueur F, Pelosini M, Garcia-Sanz R, Jurczyszyn A, Demangel D, Reis RM, Iskierka-Jażdżewska E, Markiewicz M, Gemignani F, Subocz E, Zawirska D, Druzd-Sitek A, Stępień A, Alonso MH, Sainz J, Canzian F, and Campa D

Subjects
Adult, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Polymorphism, Single Nucleotide, Prognosis, Prospective Studies, Retrospective Studies, Telomere genetics, Multiple Myeloma genetics, Telomere Homeostasis
Abstract

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 × 10 -6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.

Published
2021
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22. Inherited variation in the xenobiotic transporter pathway and survival of multiple myeloma patients.

Author

Macauda A, Castelli E, Buda G, Pelosini M, Butrym A, Watek M, Kruszewski M, Vangsted AJ, Rymko M, Jamroziak K, Abildgaard N, Haastrup EK, Mazur G, Ríos R, Jurczyszyn A, Zawirska D, Dudziński M, Raźny M, Dutka M, Tomczak W, Suska A, Druzd-Sitek A, Marques H, Petrini M, Markiewicz M, Martinez-Lopez J, Ebbesen LH, Iskierka-Jażdżewska E, Sainz J, Canzian F, and Campa D

Subjects
Aged, Constitutive Androstane Receptor, Disease-Free Survival, Drug Resistance, Neoplasm genetics, Female, Humans, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, Multiple Myeloma therapy, Retrospective Studies, Survival Rate, Carrier Proteins genetics, Linkage Disequilibrium, Multiple Myeloma genetics, Multiple Myeloma mortality, Neoplasm Proteins genetics, Polymorphism, Single Nucleotide
Abstract

Over the past four decades, remarkable progress has been made in the treatment and prognosis of multiple myeloma (MM), although it remains an incurable disease. Chemotherapy resistance is a major hurdle for treatment efficacy. Drug resistance can be innate and so driven by genes involved in the drug metabolism pathways. We performed an association study of 71 germline variants within the major genes in those pathways (ABCB1, ABCC2, ABCG2, and their regulators NR1I2/PXR and NR1I3/CAR) in the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 1365 MM cases with survival information recruited in 5 European countries. Two of the SNPs showed a significant association with the survival of MM patients, namely rs2235013, located in ABCB1 [Hazard ratio (HR) = 1·52, 95% confidence interval (CI) = 1·18-1·95, P = 0·00087], and rs4148388, located in ABCC2 (HR = 2·15, 95% CI = 1·44-3·22, P = 0·0001). ABCC2 plays an essential role in transporting various anticancer drugs, including several used against MM, out of the cell. In silico analyses predict that the variant alleles of four SNPs in linkage disequilibrium with ABCC2-rs4148388 are associated with increased gene expression. Overexpression of ABCC2 increases drug clearance and therefore may induce drug resistance mechanisms. In conclusion, we found a promising association between ABCC2-rs4148388 and MM outcome that is supported by a plausible biological explanation., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

Published
2018
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23. Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG).

Author

Wierzbowska A, Wawrzyniak E, Siemieniuk-Rys M, Kotkowska A, Pluta A, Golos A, Robak T, Szarawarska M, Jaskowiec A, Duszenko E, Rybka J, Holojda J, Grosicki S, Pienkowska-Grela B, Woroniecka R, Ejduk A, Watek M, Wach M, Mucha B, Skonieczka K, Czyzewska M, Jachalska A, Klonowska A, Iliszko M, Knopinska-Posluszny W, Jarmuz-Szymczak M, Przybylowicz-Chalecka A, Gil L, Kopacz A, Holowiecki J, and Haus O

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Combined Modality Therapy, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Poland, Prognosis, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Chromosome Aberrations, Karyotype, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Monosomy
Abstract

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK +  was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK +  treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK +  MK - and CK +  MK +  group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK - but not in MK +  group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK + .

Published
2017
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24. Identification of miRSNPs associated with the risk of multiple myeloma.

Author

Macauda A, Calvetti D, Maccari G, Hemminki K, Försti A, Goldschmidt H, Weinhold N, Houlston R, Andersen V, Vogel U, Buda G, Varkonyi J, Sureda A, Martinez Lopez J, Watek M, Butrym A, Sarasquete ME, Dudziński M, Jurczyszyn A, Druzd-Sitek A, Kruszewski M, Subocz E, Petrini M, Iskierka-Jażdżewska E, Raźny M, Szombath G, Marques H, Zawirska D, Chraniuk D, Halka J, Hove Jacobsen SE, Mazur G, García Sanz R, Dumontet C, Moreno V, Stępień A, Beider K, Pelosini M, Manuel Reis R, Krawczyk-Kulis M, Rymko M, Avet-Loiseau H, Lesueur F, Grząśko N, Ostrovsky O, Jamroziak K, Vangsted AJ, Jerez A, Tomczak W, Zaucha JM, Kadar K, Sainz J, Nagler A, Landi S, Gemignani F, and Canzian F

Subjects
3' Untranslated Regions genetics, Adult, Aged, Binding Sites genetics, Case-Control Studies, Europe, Female, Genome-Wide Association Study methods, Genotype, Humans, Male, Middle Aged, Myeloma Proteins genetics, RNA, Messenger genetics, Risk, Genetic Predisposition to Disease genetics, MicroRNAs genetics, Multiple Myeloma genetics, Polymorphism, Single Nucleotide genetics
Abstract

Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p < 0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3'UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs, we have shown promising associations with MM risk., (© 2016 UICC.)

Published
2017
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25. Corrigendum: Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.

Author

Ziv E, Dean E, Hu D, Martino A, Serie D, Curtin K, Campa D, Aftab B, Bracci P, Buda G, Zhao Y, Caswell-Jin J, Diasio R, Dumontet C, Dudziński M, Fejerman L, Greenberg A, Huntsman S, Jamroziak K, Jurczyszyn A, Kumar S, Atanackovic D, Glenn M, Cannon-Albright LA, Jones B, Lee A, Marques H, Martin T, Martinez-Lopez J, Rajkumar V, Sainz J, Juul Vangsted A, Watek M, Wolf J, Slager S, Camp NJ, Canzian F, and Vachon C

Published
2015
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