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1. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E, Noerenberg, D, Mansouri, L, Ljungström, V, Frick, M, Sutton, L-A, Blakemore, SJ, Galan-Sousa, J, Plevova, K, Baliakas, P, Rossi, D, Clifford, R, Roos-Weil, D, Navrkalova, V, Dörken, B, Schmitt, CA, Smedby, KE, Juliusson, G, Giacopelli, B, Blachly, JS, Belessi, C, Panagiotidis, P, Chiorazzi, N, Davi, F, Langerak, AW, Oscier, D, Schuh, A, Gaidano, G, Ghia, P, Xu, W, Fan, L, Bernard, OA, Nguyen-Khac, F, Rassenti, L, Li, J, Kipps, TJ, Stamatopoulos, K, Pospisilova, S, Zenz, T, Oakes, CC, Strefford, JC, Rosenquist, R, and Damm, F

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Cancer, Hematology, Rare Diseases, Lymphoma, Clinical Research, Genetics, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Adult, Aged, Early Growth Response Protein 2, Female, Genes, p53, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Mutation, Proportional Hazards Models, Clinical Sciences, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

Published
2017

2. Prospective validation of the prognostic relevance of CD34+CD38- AML stem cell frequency in the HOVON-SAKK132 trial.

Author

Ngai, L.L., Hanekamp, D., Janssen, F, Carbaat-Ham, J., Hofland, M.A.M.A., Fayed, M.M.H.E., Kelder, A., Oudshoorn-van Marsbergen, L., Scholten, W.J., Snel, A.N., Bachas, C., Tettero, J.M., Breems, D.A., Fischer, T., Gjertsen, B.T., Griškevičius, L., Juliusson, G., Loosdrecht, A.A. van de, Maertens, J.A., Manz, M.G., Pabst, T., Passweg, J.R., Porkka, K., Valk, P.J.M., Gradowska, P., Löwenberg, B., Leeuw, D.C. de, Janssen, J.J.W.M., Ossenkoppele, G.J., Cloos, J., Ngai, L.L., Hanekamp, D., Janssen, F, Carbaat-Ham, J., Hofland, M.A.M.A., Fayed, M.M.H.E., Kelder, A., Oudshoorn-van Marsbergen, L., Scholten, W.J., Snel, A.N., Bachas, C., Tettero, J.M., Breems, D.A., Fischer, T., Gjertsen, B.T., Griškevičius, L., Juliusson, G., Loosdrecht, A.A. van de, Maertens, J.A., Manz, M.G., Pabst, T., Passweg, J.R., Porkka, K., Valk, P.J.M., Gradowska, P., Löwenberg, B., Leeuw, D.C. de, Janssen, J.J.W.M., Ossenkoppele, G.J., and Cloos, J.

Abstract

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Published
2023

5. P543: TARGETING SAMHD1 WITH HYDROXYUREA IN FIRST-LINE CYTARABINE-BASED THERAPY OF NEWLY DIAGNOSED ACUTE MYELOID LEUKAEMIA: RESULTS FROM THE HEAT-AML TRIAL

Author

Jädersten, M., primary, Lilienthal, I., additional, Tsesmetzis, N., additional, Lourda, M., additional, Bengtzén, S., additional, Bohlin, A., additional, Arnroth, C., additional, Erkers, T., additional, Seashore-Ludlow, B., additional, Giraud, G., additional, Barkhordar, G. S., additional, Tao, S., additional, Fogelstrand, L., additional, Saft, L., additional, Östling, P., additional, Schinazi, R., additional, Kim, B., additional, Schaller, T., additional, Juliusson, G., additional, Deneberg, S., additional, Lehmann, S., additional, Rassidakis, G., additional, Höglund, M., additional, Henter, J.-I., additional, and Herold, N., additional

Published
2022
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6. Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Author

Ravandi, F, Kreitman, RJ, Tiacci, E, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, SA, Blachly, JS, Broccoli, A, Call, T, Chihara, D, Dearden, C, Demeter, J, Dietrich, S, Else, M, Epperla, N, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Jorgensen, J, Juliusson, G, Lauria, F, Lozanski, G, Parikh, SA, Park, JH, Polliack, A, Quest, G, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Thompson, PA, Troussard, X, Zent, CS, Zenz, T, Zinzani, PL, Woermann, B, Rai, K, Grever, M, Ravandi, F, Kreitman, RJ, Tiacci, E, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, SA, Blachly, JS, Broccoli, A, Call, T, Chihara, D, Dearden, C, Demeter, J, Dietrich, S, Else, M, Epperla, N, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Jorgensen, J, Juliusson, G, Lauria, F, Lozanski, G, Parikh, SA, Park, JH, Polliack, A, Quest, G, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Thompson, PA, Troussard, X, Zent, CS, Zenz, T, Zinzani, PL, Woermann, B, Rai, K, and Grever, M

Abstract

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

Published
2022

8. Recurrent mutations refine prognosis in chronic lymphocytic leukemia

Author

Baliakas, P, Hadzidimitriou, A, Sutton, L-A, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, L, Scarfò, L, Cortese, D, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, K, and Rosenquist, R

Published
2015
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12. Common variation at 12q24.13 (OAS3) influences chronic lymphocytic leukemia risk

Author

Sava, G P, Speedy, H E, Di Bernardo, M C, Dyer, M JS, Holroyd, A, Sunter, N J, Marr, H, Mansouri, L, Deaglio, S, Karabon, L, Frydecka, I, Jamroziak, K, Woszczyk, D, Juliusson, G, Smedby, K E, Jayne, S, Majid, A, Wang, Y, Dearden, C, Hall, A G, Mainou-Fowler, T, Jackson, G H, Summerfield, G, Harris, R J, Pettitt, A R, Allsup, D J, Bailey, J R, Pratt, G, Pepper, C, Fegan, C, Rosenquist, R, Catovsky, D, Allan, J M, and Houlston, R S

Published
2015
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14. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines

Author

Grever, M, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, S, Blachly, JS, Call, T, Cross, M, Dearden, C, Demeter, J, Dietrich, S, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Juliusson, G, Kraut, E, Kreitman, RJ, Lauria, F, Lozanski, G, Parikh, SA, Park, J, Polliack, A, Ravandi, F, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Tiacci, E, Troussard, X, Zent, C, Zenz, T, Zinzani, PL, Wormann, B, Grever, M, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, S, Blachly, JS, Call, T, Cross, M, Dearden, C, Demeter, J, Dietrich, S, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Juliusson, G, Kraut, E, Kreitman, RJ, Lauria, F, Lozanski, G, Parikh, SA, Park, J, Polliack, A, Ravandi, F, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Tiacci, E, Troussard, X, Zent, C, Zenz, T, Zinzani, PL, and Wormann, B

Abstract

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

Published
2021

16. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Author

Lowenberg, B., Pabst, T., Maertens, J., Gradowska, P., Biemond, B.J., Spertini, O., Vellenga, E., Griskevicius, L., Tick, L.W., Jongen-Lavrencic, M., Kooy, M.V., Vekemans, M.C., Velden, W.J.F.M. van der, Beverloo, B., Michaux, L., Graux, C., Deeren, D., Weerdt, O. de, Esser, J.W.J. van, Bargetzi, M., Klein, S.K., Gadisseur, A., Westerweel, P.E., Veelken, H., Gregor, M., Silzle, T., Lammeren-Venema, D. van, Moors, I., Breems, D.A., Hoogendoorn, M., Legdeur, M.C.J.C., Fischer, T., Kuball, J., Cornelissen, J., Porkka, K., Juliusson, G., Meyer, P., Hoglund, M., Gjertsen, B.T., Janssen, J.J.W.M., Huls, G., Passweg, J., Cloos, J., Valk, P.J.M., Elssen, C.H.M.J. van, Manz, M.G., Floisand, Y., Ossenkoppele, G.J., Dutch-Belgian Hemato-Oncology Coop, Swiss Grp Clinical Canc Res SAKK, Clinical Haematology, CCA - Cancer Treatment and Quality of Life, Hematology, Clinical Genetics, Dutch-Belgian Hemato-Oncology Cooperative Group, Swiss Group for Clinical Cancer Research (SAKK), Internal medicine, VU University medical center, Hematology laboratory, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Stem Cell Aging Leukemia and Lymphoma (SALL), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Oncology, Clinical Trials and Observations, Phases of clinical research, 0302 clinical medicine, Autologous stem-cell transplantation, hemic and lymphatic diseases, Medicine and Health Sciences, ELDERLY-PATIENTS, Lenalidomide, LENALIDOMIDE, Remission Induction, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Chemotherapy regimen, 3. Good health, CYTARABINE, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, Adolescent, HIGH-DOSE LENALIDOMIDE, MINIMAL RESIDUAL DISEASE, ACUTE MYELOID-LEUKEMIA, Transplantation, Autologous, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, SEQUENTIAL AZACITIDINE, Internal medicine, AZACITIDINE PLUS LENALIDOMIDE, AZACITIDINE PLUS, medicine, Humans, COMBINATION, Aged, Science & Technology, business.industry, Minimal residual disease, Transplantation, Regimen, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Cytarabine, Human medicine, business, 030215 immunology
Abstract

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study. ispartof: BLOOD ADVANCES vol:5 issue:4 pages:1110-1121 ispartof: location:United States status: published

Published
2020

40. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(Immuno)therapy

Author

Baliakas, P. Mattsson, M. Hadzidimitriou, A. Minga, E. Agathangelidis, A. Sutton, L.-A. Scarfo, L. Davis, Z. Yan, X.-J. Plevova, K. Sandberg, Y. Vojdeman, F.J. Tzenou, T. Chu, C.C. Veronese, S. Mansouri, L. Smedby, K.E. Giudicelli, V. Nguyen-Khac, F. Panagiotidis, P. Juliusson, G. Anagnostopoulos, A. Lefranc, M.-P. Trentin, L. Catherwood, M. Montillo, M. Niemann, C.U. Langerak, A.W. Pospisilova, S. Stavroyianni, N. Chiorazzi, N. Oscier, D. Jelinek, D.F. Shanafelt, T. Darzentas, N. Belessi, C. Davi, F. Ghia, P. Rosenquist, R. Stamatopoulos, K.

Published
2018

41. S1614 CHROMOSOMAL ABNORMALITIES DETERMINE OUTCOME IN NPM1MUT/FLT3-ITDNEG/LOW ACUTE MYELOID LEUKEMIA

Author

Angenendt, L., primary, Röllig, C., additional, Montesinos, P., additional, Martínez-Cuadrón, D., additional, Barragan, E., additional, García, R., additional, Botella, C., additional, Martínez, P., additional, Ravandi, F., additional, Kadia, T., additional, Kantarjian, H.M., additional, Cortes, J., additional, Juliusson, G., additional, Lazarevic, V., additional, Höglund, M., additional, Lehmann, S., additional, Recher, C., additional, Pigneux, A., additional, Bertoli, S., additional, Dumas, P.-Y., additional, Dombret, H., additional, Preudhomme, C., additional, Micol, J.-B., additional, Terré, C., additional, Ráčil, Z., additional, Novák, J., additional, Žák, P., additional, Wei, A.H., additional, Tiong, I.S., additional, Wall, M., additional, Estey, E., additional, Shaw, C., additional, Exeler, R., additional, Wagenführ, L., additional, Stölzel, F., additional, Thiede, C., additional, Stelljes, M., additional, Lenz, G., additional, Mikesch, J.-H., additional, Serve, H., additional, Ehninger, G., additional, Berdel, W.E., additional, Kramer, M., additional, Krug, U., additional, and Schliemann, C., additional

Published
2019
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43. PS1032 SURVIVAL FROM ACUTE MYELOID LEUKEMIA HAS SINCE 1997 IMPROVED ONLY IN MALES AGED 50–75 YEARS – A SWEDISH POPULATION-BASED STUDY

Author

Juliusson, G., primary, Hagberg, O., additional, Lazarevic, V., additional, Lorenz, F., additional, Ölander, E., additional, Antunovic, P., additional, Cammenga, J., additional, Wennström, L., additional, Möllgård, L., additional, Brune, M., additional, Deneberg, S., additional, Derolf, Å., additional, Lehmann, S., additional, and Höglund, M., additional

Published
2019
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44. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(Immuno)therapy

Author

Baliakas, P. (P.), Mattsson, M. (Mattias), Hadzidimitriou, A. (A.), Minga, E. (Evangelia), Agathangelidis, A. (Andreas), Sutton, L.-A. (L.), Scarfó, L. (L.), Davis, Z. (Zadie), Yan, X.-J. (Xiao-Jie), Plevova, K. (K.), Sandberg, Y. (Yorick), Vojdeman, F.J. (Fie Juhl), Tzenou, T. (T.), Chu, C.C. (Charles C.), Veronese, S. (Silvio), Mansouri, A. (Ahmed), Smedby, O., Giudicelli, V. (Veronique), Nguyen-Khac, F. (Florence), Panagiotidis, P. (P.), Juliusson, G. (Gunnar), Anagnostopoulos, C. (Constantinos), Lefranc, M.-P. (Marie-Paule), Trentin, L. (Livio), Catherwood, M. (M.), Montillo, M. (Marco), Niemann, C.U. (Carsten U.), Langerak, A.W. (Anton), Pospisilova, S. (Sarka), Stavroyianni, N. (Niki), Chiorazzi, N. (Nicholas), Oscier, D.G. (David Graham), Jelinek, D.F. (Diane F.), Shanafelt, T. (Tait), Darzentas, N. (Nikos), Belessi, C. (C.), Davi, F. (Frédéric), Ghia, P. (Paolo), Rosenquist, R. (R.), Stamatopoulos, K. (Kostas), Baliakas, P. (P.), Mattsson, M. (Mattias), Hadzidimitriou, A. (A.), Minga, E. (Evangelia), Agathangelidis, A. (Andreas), Sutton, L.-A. (L.), Scarfó, L. (L.), Davis, Z. (Zadie), Yan, X.-J. (Xiao-Jie), Plevova, K. (K.), Sandberg, Y. (Yorick), Vojdeman, F.J. (Fie Juhl), Tzenou, T. (T.), Chu, C.C. (Charles C.), Veronese, S. (Silvio), Mansouri, A. (Ahmed), Smedby, O., Giudicelli, V. (Veronique), Nguyen-Khac, F. (Florence), Panagiotidis, P. (P.), Juliusson, G. (Gunnar), Anagnostopoulos, C. (Constantinos), Lefranc, M.-P. (Marie-Paule), Trentin, L. (Livio), Catherwood, M. (M.), Montillo, M. (Marco), Niemann, C.U. (Carsten U.), Langerak, A.W. (Anton), Pospisilova, S. (Sarka), Stavroyianni, N. (Niki), Chiorazzi, N. (Nicholas), Oscier, D.G. (David Graham), Jelinek, D.F. (Diane F.), Shanafelt, T. (Tait), Darzentas, N. (Nikos), Belessi, C. (C.), Davi, F. (Frédéric), Ghia, P. (Paolo), Rosenquist, R. (R.), and Stamatopoulos, K. (Kostas)

Published
2018
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45. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, Stamatopoulos, K, Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, and Stamatopoulos, K

Published
2018

46. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E. Noerenberg, D. Mansouri, L. Ljungström, V. Frick, M. Sutton, L.-A. Blakemore, S.J. Galan-Sousa, J. Plevova, K. Baliakas, P. Rossi, D. Clifford, R. Roos-Weil, D. Navrkalova, V. Dörken, B. Schmitt, C.A. Smedby, K.E. Juliusson, G. Giacopelli, B. Blachly, J.S. Belessi, C. Panagiotidis, P. Chiorazzi, N. Davi, F. Langerak, A.W. Oscier, D. Schuh, A. Gaidano, G. Ghia, P. Xu, W. Fan, L. Bernard, O.A. Nguyen-Khac, F. Rassenti, L. Li, J. Kipps, T.J. Stamatopoulos, K. Pospisilova, S. Zenz, T. Oakes, C.C. Strefford, J.C. Rosenquist, R. Damm, F.

Abstract

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Published
2017

47. Early death rates remain high in high-risk APL : update from the Swedish Acute Leukemia Registry 1997-2013

Author

Lehmann, Sören, Deneberg, S., Antunovic, P., Rangert-Derolf, A., Garelius, H., Lazarevic, V., Myhr-Eriksson, K., Möllgård, L., Uggla, B., Wahlin, A., Wennstrom, L., Höglund, Martin, Juliusson, G., Lehmann, Sören, Deneberg, S., Antunovic, P., Rangert-Derolf, A., Garelius, H., Lazarevic, V., Myhr-Eriksson, K., Möllgård, L., Uggla, B., Wahlin, A., Wennstrom, L., Höglund, Martin, and Juliusson, G.

Published
2017
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48. Prevalence and characteristics of survivors from acute myeloid leukemia in Sweden

Author

Juliusson, G., Abrahamsson, J., Lazarevic, V., Antunovic, P., Derolf, A., Garelius, H., Lehmann, S., Myhr-Eriksson, K., Mollgard, L., Uggla, B., Wåhlin, Anders, Wennstrom, L., Hoglund, M., Juliusson, G., Abrahamsson, J., Lazarevic, V., Antunovic, P., Derolf, A., Garelius, H., Lehmann, S., Myhr-Eriksson, K., Mollgard, L., Uggla, B., Wåhlin, Anders, Wennstrom, L., and Hoglund, M.

Published
2017
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