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Different prognosti...
Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
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- Mansouri, L (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Thorvaldsdottir, B (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Sutton, LA (author)
- Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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show more...
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- Karakatsoulis, G (author)
- Inst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece.;Univ Ioannina, Dept Math, Ioannina, Greece.
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- Meggendorfer, M (author)
- MLL Munich Leukemia Lab, Munich, Germany.
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- Parker, H (author)
- Univ Southampton, Fac Med, Sch Canc Sci, Canc Genom, Southampton, England.
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- Nadeu, F (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.,Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Serv Hematol Clin, Paris, France.
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- Brieghel, C (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark.
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- Laidou, S (author)
- Inst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece.
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- Moia, R (author)
- Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy.
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- Rossi, D (author)
- Oncol Inst Southern Switzerland, Div Hematol, Bellinzona, Switzerland.;Inst Oncol Res, Lab Expt Hematol, Bellinzona, Switzerland.
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- Catherwood, M (author)
- Queens Univ Belfast, Patrick G Johnston Ctr Canc Res, Belfast, Antrim, North Ireland.
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- Kotaskova, J (author)
- Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.
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- Delgado, J (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain.
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- Rodriguez-Vicente, AE (author)
- Univ Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain.
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- Benito, R (author)
- Univ Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain.
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- Mattsson, Mattias (author)
- Uppsala universitet,Cancerprecisionsmedicin
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- Bonfiglio, S (author)
- Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy.
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- Scarfo, L (author)
- Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy.
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Mattsson, M (author)
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- Davis, Z (author)
- Univ Hosp Dorset, Mol Pathol Dept, Bournemouth, Dorset, England.
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- Gogia, A (author)
- All India Inst Med Sci AIIMS, New Delhi, India.
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- Rani, L (author)
- All India Inst Med Sci AIIMS, New Delhi, India.
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- Baliakas, Panagiotis, 1977- (author)
- Uppsala universitet,Cancerprecisionsmedicin
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- Foroughi-Asl, H (author)
- Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Jylha, C (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Skaftason, A (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Rapado, I (author)
- Hosp Univ 12 Octubre, Madrid, Spain.
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- Miras, F (author)
- Hosp Univ 12 Octubre, Madrid, Spain.
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- Martinez-Lopez, J (author)
- Hosp Univ 12 Octubre, Madrid, Spain.;Spanish Natl Canc Res CNIO, Madrid, Spain.
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- de la Serna, J (author)
- Hosp Univ 12 Octubre, Madrid, Spain.;Spanish Natl Canc Res CNIO, Madrid, Spain.
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Rivas, JMH (author)
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- Thornton, P (author)
- Beaumont Hosp, Haematol Dept, Dublin, Ireland.
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- Larrayoz, MJ (author)
- Univ Navarra, Hematol Dis Lab, CIMA LAB Diagnost, Pamplona, Spain.;Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain.
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- Calasanz, MJ (author)
- Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain.
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- Fesus, V (author)
- Semmelweis Univ, Dept Pathol & Expt Canc Res, HCEMM SE Mol Oncohematol Res Grp, Budapest, Hungary.
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- Matrai, Z (author)
- Cent Hosp Southern Pest, Natl Inst Hematol & Infect Dis, Budapest, Hungary.
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- Bodor, C (author)
- Semmelweis Univ, Dept Pathol & Expt Canc Res, HCEMM SE Mol Oncohematol Res Grp, Budapest, Hungary.
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- Smedby, KE (author)
- Karolinska Institutet,Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden.
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- Espinet, B (author)
- Hosp Mar, Dept Pathol, Mol Cytogenet Lab, Barcelona, Spain.;Hosp Mar Res Inst IMIM, Translat Res Hematol Neoplasms Grp, Barcelona, Spain.
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- Puiggros, A (author)
- Hosp Mar, Dept Pathol, Mol Cytogenet Lab, Barcelona, Spain.;Hosp Mar Res Inst IMIM, Translat Res Hematol Neoplasms Grp, Barcelona, Spain.
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- Gupta, R (author)
- All India Inst Med Sci AIIMS, New Delhi, India.
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- Bullinger, L (author)
- Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.
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- Bosch, F (author)
- Univ Autonoma Barcelona, Hosp Univ Vall dHebron HUVH, Vall dHebron Inst Oncol VHIO, Dept Hematol,Expt Hematol,Dept Med, Barcelona, Spain.
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- Tazon-Vega, B (author)
- Univ Autonoma Barcelona, Hosp Univ Vall dHebron HUVH, Vall dHebron Inst Oncol VHIO, Dept Hematol,Expt Hematol,Dept Med, Barcelona, Spain.
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- Baran-Marszak, F (author)
- Hop Avicenne, AP HP, Serv Hematol Biol, Bobigny, France.
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Oscier, D (author)
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N'Guyen-Khac, F (author)
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- Zenz, T (author)
- Univ Hosp, Dept Oncol & Haematol, Zurich, Switzerland.;Univ Zurich, Zurich, Switzerland.
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- Terol, MJ (author)
- Univ Valencia, Dept Hematol, INCL Res Inst, Valencia, Spain.
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- Cuneo, A (author)
- Univ Ferrara, Dept Med Sci, Hematol, Ferrara, Italy.
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- Hernandez-Sanchez, M (author)
- Univ Salamanca, Canc Res Ctr IBMCC, CSIC, Salamanca, Spain.;Inst Invest Biomed IBSAL, Salamanca, Spain.;Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain.
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- Pospisilova, S (author)
- Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.
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Mills, K (author)
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- Gaidano, G (author)
- Univ Piemonte Orientale, Dept Translat Med, Div Hematol, Novara, Italy.
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- Niemann, CU (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark.
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- Campo, E (author)
- Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Ctr Invest Biomeed Red Canc CIBERONC, Madrid, Spain.;Hosp Clin Barcelona, Barcelona, Spain.;Univ Barcelona, Barcelona, Spain.
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- Strefford, JC (author)
- Univ Southampton, Fac Med, Sch Canc Sci, Canc Genom, Southampton, England.
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- Ghia, P (author)
- Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Osped San Raffaele, Milan, Italy.
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- Stamatopoulos, K (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Inst Appl Biosci, Ctr Res & Technol Hellas, Thessaloniki, Greece.
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- Rosenquist, R (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Solna, Sweden.
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Karolinska Institutet Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden (creator_code:org_t)
- 2022-12-24
- 2023
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 37:2, s. 339-347
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Abstract
Subject headings
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- Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Leukemia
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To the university's database
- By the author/editor
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Mansouri, L
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Thorvaldsdottir, ...
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Sutton, LA
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Karakatsoulis, G
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Meggendorfer, M
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Parker, H
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show more...
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Nadeu, F
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Brieghel, C
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Laidou, S
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Moia, R
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Rossi, D
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Catherwood, M
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Kotaskova, J
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Delgado, J
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Rodriguez-Vicent ...
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Benito, R
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Mattsson, Mattia ...
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Bonfiglio, S
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Scarfo, L
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Mattsson, M
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Davis, Z
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Gogia, A
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Rani, L
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Baliakas, Panagi ...
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Foroughi-Asl, H
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Jylha, C
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Skaftason, A
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Rapado, I
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Miras, F
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Martinez-Lopez, ...
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de la Serna, J
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Rivas, JMH
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Thornton, P
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Larrayoz, MJ
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Calasanz, MJ
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Fesus, V
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Matrai, Z
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Bodor, C
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Smedby, KE
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Espinet, B
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Puiggros, A
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Gupta, R
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Bullinger, L
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Bosch, F
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Tazon-Vega, B
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Baran-Marszak, F
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Oscier, D
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N'Guyen-Khac, F
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Zenz, T
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Terol, MJ
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Cuneo, A
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Hernandez-Sanche ...
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Pospisilova, S
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Mills, K
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Gaidano, G
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Niemann, CU
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Campo, E
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Strefford, JC
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Ghia, P
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Stamatopoulos, K
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Rosenquist, R
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Cancer and Oncol ...
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Leukemia
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Karolinska Institutet
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Uppsala University