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1. Author Correction: Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2022
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2. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2021
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5. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia (vol 13, 2, 2022)

Author

Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhauser, Martin, Rollig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenfuhr, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, Jose, Gomez-Segui, Ines, Cluzeau, Thomas, Moreilhon, Chimene, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Herve, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsan, Szilvia, Bodor, Csaba, Stolzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2022

6. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Lin, Wei-Yu, primary, Fordham, Sarah E, additional, Hungate, Eric, additional, Sunter, Nicola J, additional, Elstob, Claire, additional, Xu, Yaobo, additional, Park, Catherine, additional, Quante, Anne, additional, Strauch, Konstantin, additional, Gieger, Christian, additional, Skol, Andrew, additional, Rahman, Thahira, additional, Sucheston-Campbell, Lara, additional, Wang, Junke, additional, Hahn, Theresa, additional, Clay-Gilmour, Alyssa I, additional, Jones, Gail L, additional, Marr, Helen J, additional, Jackson, Graham H, additional, Menne, Tobias, additional, Collin, Mathew, additional, Ivey, Adam, additional, Hills, Robert K, additional, Burnett, Alan K, additional, Russell, Nigel H, additional, Fitzgibbon, Jude, additional, Larson, Richard A, additional, Le Beau, Michelle M, additional, Stock, Wendy, additional, Heidenreich, Olaf, additional, Alharbi, Abrar, additional, Allsup, David J, additional, Houlston, Richard S, additional, Norden, Jean, additional, Dickinson, Anne M, additional, Douglas, Elisabeth, additional, Lendrem, Clare, additional, Daly, Ann K, additional, Palm, Louise, additional, Piechocki, Kim, additional, Jeffries, Sally, additional, Bornhäuser, Martin, additional, Röllig, Christoph, additional, Altmann, Heidi, additional, Ruhnke, Leo, additional, Kunadt, Desiree, additional, Wagenführ, Lisa, additional, Cordell, Heather J, additional, Darlay, Rebecca, additional, Andersen, Mette K, additional, Fontana, Maria C, additional, Martinelli, Giovanni, additional, Marconi, Giovani, additional, Sanz, Miguel A, additional, Cervera, José, additional, Gómez-Seguí, Inés, additional, Cluzeau, Thomas, additional, Moreilhon, Chimène, additional, Raynaud, Sophie, additional, Sill, Heinz, additional, Voso, Maria Teresa, additional, Lo-Coco, Francesco, additional, Dombret, Hervé, additional, Cheok, Meyling, additional, Preudhomme, Claude, additional, Gale, Rosemary E, additional, Linch, David, additional, Gaal-Wesinger, Julia, additional, Masszi, Andras, additional, Nowak, Daniel, additional, Hofmann, Wolf-Karsten, additional, Gilkes, Amanda, additional, Porkka, Kimmo, additional, Milosevic Feenstra, Jelena D, additional, Kralovics, Robert, additional, Grimwade, David, additional, Meggendorfer, Manja, additional, Haferlach, Torsten, additional, Krizsán, Szilvia, additional, Bödör, Csaba, additional, Stölzel, Friedrich, additional, Onel, Kenan, additional, and Allan, James M, additional

Published
2021
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9. Profiling Tissue and Biofluid miR-155-5p, miR-155*, and miR-146a-5p Expression in Graft vs. Host Disease.

Author

Crossland, Rachel E., Norden, Jean, Ghimire, Sakhila, Juric, Mateja Kralj, Pearce, Kim F., Lendrem, Clare, Collin, Matthew, Mischak-Weissinger, Eva, Holler, Ernst, Greinix, Hildegard T., and Dickinson, Anne M.

Subjects
VESICLES (Cytology), SKIN biopsy, EXTRACELLULAR vesicles, URINE, PATHOLOGICAL physiology
Abstract

Introduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes. Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival. Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p < 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02). Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level. [ABSTRACT FROM AUTHOR]

Published
2021
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11. Genetic Association of Hematopoietic Stem Cell Transplantation Outcome beyond Histocompatibility Genes

Author

Gam, Rihab, Shah, Pranali, Crossland, Rachel E., Norden, Jean, Dickinson, Anne M., and Dressel, Ralf

Subjects
miR-146a, non-human leukocyte antigen single-nucleotide polymorphisms, regulatory networks, surgical procedures, operative, MICA, gene expression profiling, regulatory networks, non-human leukocyte antigen single-nucleotide polymorphisms, microRNAs, forkheadbox protein 3, miR-155, miR-146a, MICA, Immunology, gene expression profiling, forkheadbox protein 3, Review, microRNAs, miR-155
Abstract

The outcome of hematopoietic stem cell transplantation (HSCT) is controlled by genetic factors among which the leukocyte antigen human leukocyte antigen (HLA) matching is most important. In addition, minor histocompatibility antigens and non-HLA gene polymorphisms in genes controlling immune responses are known to contribute to the risks associated with HSCT. Besides single-nucleotide polymorphisms (SNPs) in protein coding genes, SNPs in regulatory elements such as microRNAs (miRNAs) contribute to these genetic risks. However, genetic risks require for their realization the expression of the respective gene or miRNA. Thus, gene and miRNA expression studies may help to identify genes and SNPs that indeed affect the outcome of HSCT. In this review, we summarize gene expression profiling studies that were performed in recent years in both patients and animal models to identify genes regulated during HSCT. We discuss SNP– mRNA–miRNA regulatory networks and their contribution to the risks associated with HSCT in specific examples, including forkheadbox protein 3 and regulatory T cells, the role of the miR-155 and miR-146a regulatory network for graft-versus-host disease, and the function of MICA and its receptor NKG2D for the outcome of HSCT. These examples demonstrate how SNPs affect expression or function of proteins that modulate the alloimmune response and influence the outcome of HSCT. Specific miRNAs targeting these genes and directly affecting expression of mRNAs are identified. It might be valuable in the future to determine SNPs and to analyze miRNA and mRNA expression in parallel in cohorts of HSCT patients to further elucidate genetic risks of HSCT. Open-Access-Publikationsfonds 2017 peerReviewed

Published
2017

12. The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation

Author

Norden, Jean, primary, Pearce, Kim F., additional, Irving, Julie A. E., additional, Collin, Matthew P., additional, Wang, Xiao N., additional, Wolff, Daniel, additional, Kolb, Hans-Jochem, additional, Socie, Gerard, additional, Kuzmina, Zoya, additional, Greinix, Hildegard, additional, Holler, Ernst, additional, Rocha, Vanderson, additional, Gluckman, Eliane, additional, Hromadnikova, Ilona, additional, and Dickinson, Anne M., additional

Published
2018
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13. Differential MicroRNA Expression Levels in Cutaneous Acute Graft-Versus-Host Disease

Author

Atarod, Sadaf, primary, Norden, Jean, additional, Bibby, Louis A., additional, Janin, Anne, additional, Ratajczak, Philippe, additional, Lendrem, Clare, additional, Pearce, Kim F., additional, Wang, Xiao-Nong, additional, O’Reilly, Steven, additional, Van Laar, Jacob M., additional, Collin, Matthew, additional, Dickinson, Anne M., additional, and Crossland, Rachel E., additional

Published
2018
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26. Prognostic significance of interleukin-7 receptor-α gene polymorphisms in allogeneic stem-cell transplantation: a confirmatory study

Author

Shamim, Zaiba, Ryder, Lars P, Christensen, Ib J, Toubert, Antoine, Norden, Jean, Collin, Matthew, Jackson, Graham, Dickinson, Anne M, Müller, Klaus, Shamim, Zaiba, Ryder, Lars P, Christensen, Ib J, Toubert, Antoine, Norden, Jean, Collin, Matthew, Jackson, Graham, Dickinson, Anne M, and Müller, Klaus

Abstract

BACKGROUND: Interleukin-7 (IL-7) is a hematopoietic cytokine essential for T-cell development in the thymus and for the maintenance of peripheral T cells. A previous study of single nucleotide polymorphisms in the exons of IL-7 receptor a-chain (IL-7Ra) in a Danish cohort of patients undergoing allogeneic stem-cell transplantation (SCT) identified donor genotype GG at rs1494555 as a risk factor for treatment-related mortality (TRM) after SCT. METHODS: In this validation study, 116 British and French SCT patients and their donors were investigated by sequence-specific primer polymerase chain reaction. RESULTS: Both donor rs1494555GG genotype and the tightly coupled rs1494558TT genotype were significantly associated with grade 3 to 4 acute graft versus host disease. Although both genotypes tended to be associated with increased TRM, this did not translate into altered overall survival. CONCLUSION: The present data indicate that the IL-7 pathway is associated with alloreactivity in SCT, which is in line with the previously observed association between IL-7Ra single nucleotide polymorphisms and TRM.

Published
2011

29. Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

Author

Novota, Peter, primary, Zinöcker, Severin, additional, Norden, Jean, additional, Wang, Xiao Nong, additional, Sviland, Lisbet, additional, Opitz, Lennart, additional, Salinas-Riester, Gabriela, additional, Rolstad, Bent, additional, Dickinson, Anne M., additional, Walter, Lutz, additional, and Dressel, Ralf, additional

Published
2011
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30. Clinical and Genetic Risk Assessment for Overall Survival in Haematopoietic Stem Cell Transplantation (HSCT).

Author

Dickinson, Anne M, primary, Pearce, Kim F, additional, Jackson, Graham H, additional, Collin, Matthew, additional, Norden, Jean, additional, Holler, Ernst, additional, Bickeboller, Heike, additional, Balavarca, Yesilda, additional, Rocha, Vanderson, additional, Kolb, Hans-Jochem, additional, Aubano, Alvaro, additional, Hromadnikova, Ilona, additional, Sedlacek, Petr, additional, and Gratwohl, Alois, additional

Published
2009
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32. A Distinct Pattern of Non-HLA Polymorphisms Predicts an Increased Risk for GvHD without Benefit of GvL in HLA Matched Sibling Transplants for Chronic Myeloid Leukemia (CML).

Author

Dickinson, Anne M., primary, Pearce, Kim F., additional, Norden, Jean, additional, Neylor, A., additional, Holler, Ernst, additional, Rocha, Vanderson, additional, Gluckman, Eliane, additional, Kolb, Hans-Jochem, additional, Hromadnikova, Ilona, additional, Sedlacek, Petr, additional, Niederwieser, Dietger W., additional, Brand, Ronald, additional, Ruutu, Tapani, additional, Apperley, Jane, additional, Goulmy, E.A.J.M., additional, Olavarria, Eduardo, additional, de Witte, T.M., additional, Roosnek, Eddy, additional, Siegert, Wolfgang, additional, and Gratwohl, Alois, additional

Published
2006
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35. Prognostic Significance of Interleukin-7 Receptor- Gene Polymorphisms in Allogeneic Stem-Cell Transplantation A Confirmatory Study

Author

Shamim, Zaiba, Ryder, Lars P., Christensen, Ib J., Toubert, Antoine, Norden, Jean, Collin, Matthew, Jackson, Graham, Dickinson, Anne M., and Müller, Klaus

Abstract

Interleukin-7 (IL-7) is a hematopoietic cytokine essential for T-cell development in the thymus and for the maintenance of peripheral T cells. A previous study of single nucleotide polymorphisms in the exons of IL-7 receptor -chain (IL-7R) in a Danish cohort of patients undergoing allogeneic stem-cell transplantation (SCT) identified donor genotype GG at rs1494555 as a risk factor for treatment-related mortality (TRM) after SCT.

Published
2011
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37. Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia.

Author

Pearce KF, Lee SJ, Haagenson M, Petersdorf EW, Norden J, Collin MP, Klein JP, Spellman SR, Lowerson SA, Davies S, and Dickinson AM

Subjects
Adolescent, Adult, Female, Graft vs Host Disease prevention & control, HLA Antigens genetics, HLA Antigens immunology, Histocompatibility immunology, Histocompatibility Testing, Humans, Interleukin-10 genetics, Interleukin-10 immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Myeloablative Agonists administration & dosage, Polymorphism, Genetic, Receptors, Interleukin-1 Type II genetics, Receptors, Interleukin-1 Type II immunology, Receptors, Tumor Necrosis Factor, Type II genetics, Receptors, Tumor Necrosis Factor, Type II immunology, Recurrence, Risk Factors, Survival Analysis, Transplantation, Homologous, Unrelated Donors, Hematopoietic Stem Cell Transplantation, Histocompatibility genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Abstract

Background: Allogeneic hematopoietic cell transplantation is the main curative therapy for patients with chronic myeloid leukemia who do not respond to tyrosine kinase inhibitors. It has been proposed that non-human leukocyte antigen gene polymorphisms influence outcome after hematopoietic cell transplantation and could be used alongside traditional patient-donor and transplant characteristics to create a recipient risk profile associated with allogeneic hematopoietic cell transplantation., Design and Methods: A previous study from the European Group for Blood and Marrow Transplantation showed that the absence of recipient tumor necrosis factor receptor II, absence of donor interleukin 10 ATA/ACC and presence of donor interleukin 1 receptor antagonist allele 2 genotypes were associated with decreased survival and increased non-relapse mortality in adult patients with chronic myeloid leukemia undergoing myeloablative human leukocyte antigen-identical sibling transplantation. To explore these associations in unrelated donor transplantation, these polymorphisms were genotyped in 383 adult patients with chronic myeloid leukemia who underwent hematopoietic cell transplantation from unrelated donors matched for 10/10 human leukocyte antigens., Results: The polymorphisms were not associated with overall survival, non-relapse mortality, relapse or acute graft-versus-host disease in the unrelated donor cohort. Comparison of the unrelated donor and human leukocyte antigen-identical sibling cohorts showed differences in survival and clinical characteristics., Conclusions: We did not confirm that non-human leukocyte antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia, possibly because of the strong association between clinical variables and outcome which masked more subtle genetic effects.

Published
2012
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38. Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia.

Author

Dickinson AM, Pearce KF, Norden J, O'Brien SG, Holler E, Bickeböller H, Balavarca Y, Rocha V, Kolb HJ, Hromadnikova I, Sedlacek P, Niederwieser D, Brand R, Ruutu T, Apperley J, Szydlo R, Goulmy E, Siegert W, de Witte T, and Gratwohl A

Subjects
Adolescent, Adult, Cohort Studies, Cytokines genetics, Female, Genotype, Graft vs Host Disease genetics, Graft vs Host Disease mortality, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Prospective Studies, Risk Factors, Survival Rate trends, Treatment Outcome, Young Adult, Genomic Instability, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive surgery, Polymorphism, Single Nucleotide genetics
Abstract

Background: Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate., Design and Methods: In this study, we assessed the effect of single nucleotide polymorphisms in genes for interleukin 1 receptor antagonist (IL1RN), interleukin 4 (IL4), interleukin 6 (IL6), interleukin 10 (IL10), interferon (IFNG), tumor necrosis factor (TNF) and the cell surface receptors tumor necrosis factor receptor II (TNFRSFIB), vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) in a homogeneous cohort of 228 HLA identical sibling transplants for chronic myeloid leukemia. Three good predictors of overall survival, identified via statistical methods including Cox regression analysis, were investigated for their effects on transplant-related mortality and relapse. Predictive power was assessed after integration into the established European Group for Blood and Marrow Transplantation (EBMT) risk score., Results: Absence of patient TNFRSFIB 196R, absence of donor IL10 ATA/ACC and presence of donor IL1RN allele 2 genotypes were associated with increased transplantation-related mortality and decreased survival. Application of prediction error and concordance index statistics gave evidence that integration improved the EBMT risk score., Conclusions: Non-HLA genotypes were associated with survival after allogeneic hematopoietic stem cell transplantation. When three genetic polymorphisms were added into the EBMT risk model they improved the goodness of fit. Non-HLA genotyping could, therefore, be used to improve donor selection algorithms and risk assessment prior to allogeneic hematopoietic stem cell transplantation.

Published
2010
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