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Chronic Myeloproliferative Neoplasias

Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein

Leukemia volume 25, pages 629–637 (2011)Cite this article

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Abstract

BMI-1 and EZH2 are polycomb group (PcG) proteins that maintain self-renewal of stem cells, and are overexpressed in leukemia. To investigate the potential of PcG proteins as leukemia-associated antigens, and as targets for graft-versus-leukemia (GVL) effects, we studied cells obtained from 86 patients with chronic myeloid leukemia (CML) and 25 human leukocyte antigen (HLA)-A*0201+ sibling donors collected before allogeneic stem cell transplantation (SCT). Although BMI-1 overexpression in CD34+ cells of CML patients treated with pharmacotherapy is associated with poor prognosis, we found, conversely, that in CML patients treated with SCT, a higher expression of BMI-1, and correspondingly a lower expression of its target for repression, CDKN2A, is associated with improved leukemia-free survival. Cytotoxic T-lymphocyte (CTL) responses to the BMI-1 peptide were detected in 5 of 25 (20%) donors, and in 8 of 19 (42%) HLA-A*0201+ CML patients. BMI-1 generated more total and high-avidity immune responses, and was more immunogenic than EZH2. PcG-specific CTLs had a memory phenotype, were readily expanded in short-term cultures and were detected after SCT in recipients of PcG-specific CTL-positive donors. A higher BMI-1 expression in CML CD34+ progenitors was associated with native BMI-1 immune responses. These immune responses to PcG proteins may target leukemia stem cells and have relevance for disease control by GVL.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health, at the NHLBI.

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Author notes

  1. B N Savani

    Present address: 3Current address: Vanderbilt University VAMC Transplant Program, Nashville, TN, USA.,

  2. K Rezvani

    Present address: 4Current address: Department of Haematology, Imperial College London, Hammersmith Hospital, London, UK.,

Authors and Affiliations

  1. Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    A S M Yong, N Stephens, G Weber, B N Savani, R Eniafe, K Keyvanfar, K Rezvani & A J Barrett

  2. Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Y Li & R Kurlander

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Yong, A., Stephens, N., Weber, G. et al. Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein. Leukemia 25, 629–637 (2011). https://doi.org/10.1038/leu.2010.325

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