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. 2018 Aug 10;9:3194. doi: 10.1038/s41467-018-05211-7

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — Function of CRT-binding site in multiple malignancies and hematopoiesis. a, b In vivo tumorigenicity of cancer cells treated with neuraminidase. HL60 and DLD-1 cells were treated with heat inactivated neuraminidase (Δneu) or neuraminidase (neu), and injected subcutaneously into NSG mice. Growth of transplanted tumors was monitored by bioluminescence imaging. Tumor growth was normalized to bioluminescence signals of the injection day as fold changes. n = 5. *P < 0.05, **P < 0.01 (t-test) for tumor growth between heat inactivated neuraminidase (Δneu)- and neuraminidase (neu)-treated groups. Error bars represent standard deviation. c–f Genes related to the regulation of CRT-binding sites as a diagnostic marker for overall survival of cancer patients. Higher expression of NEU2 and NEU4 which induce the removal of sialic acids correlated with an improved survival while higher expression of ST3GAL1 and ST6GAL1 which enhance sialic acid expression correlated with a worse outcome. g Correlation between PHA-L binding and CRT levels on the cell surface of hematopoietic stem cells (HSC), Multipotential progenitor (MPP), leukemia stem cells (LSC), and blasts cells from primary AML patient samples; analysis by flow cytometry. In g, MFI, mean fluorescence intensity