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Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival
To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fracti...
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| Published in: | Experimental hematology 2015-03, Vol.43 (3), p.215-222.e2 |
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| container_end_page | 222.e2 |
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| container_title | Experimental hematology |
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| creator | Folkerts, Hendrik Hazenberg, Carin L.E Houwerzijl, Ewout J van den Heuvel, Fiona A.J Mulder, André B van der Want, Johannes J.L Vellenga, Edo |
| description | To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis ( |
| doi_str_mv | 10.1016/j.exphem.2014.11.005 |
| format | article |
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We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (<3%) based on ultrastructural characteristics and immunogold labeling for activated caspase-3. After 24 h in culture, myelodysplastic erythroblasts exhibited a significant increase in apoptosis (22 ± 7% vs. 3 ± 2%, p = 0.001). In contrast, the myelodysplastic erythroblasts from the hematon fraction did not exhibit an increased tendency toward apoptosis after culture (7 ± 3.3% vs. 1.8 ± 2.3%), which was in line with results for normal bone marrow cells. The same dependency on the micro-environment was noted for immature erythroid progenitor cells. Myelodysplastic hematons exhibited distinct numbers of erythroid burst-forming units in association with an extensive network of stromal cells, whereas small numbers of erythroid burst-forming units were generated from the myelodysplastic mononuclear cells compared with normal mononuclear cells (10.2 ± 9 vs. 162 ± 125, p < 0.001). Co-culture of erythroid myelodysplastic cells in the presence of growth factors (vascular endothelial growth factor, leukemia inhibitory factor) or on the MS-5 stromal layer did not restore the expansion of erythroid precursor cells. These data indicate that surviving myelodysplastic erythroid progenitors become more vulnerable to programmed cell death when they are detached from their own micro-environment.</description><identifier>ISSN: 0301-472X</identifier><identifier>EISSN: 1873-2399</identifier><identifier>DOI: 10.1016/j.exphem.2014.11.005</identifier><identifier>PMID: 25462021</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Advanced Basic Science ; Aged ; Aged, 80 and over ; Apoptosis ; Cell Survival ; Cells, Cultured ; Erythroid Precursor Cells - pathology ; Erythroid Precursor Cells - physiology ; Female ; Flow Cytometry ; Hematology, Oncology and Palliative Medicine ; Humans ; Leukocytes, Mononuclear - pathology ; Male ; Middle Aged ; Myelodysplastic Syndromes - physiopathology ; Real-Time Polymerase Chain Reaction ; Risk Factors ; Tumor Microenvironment</subject><ispartof>Experimental hematology, 2015-03, Vol.43 (3), p.215-222.e2</ispartof><rights>ISEH - International Society for Experimental Hematology</rights><rights>2015 ISEH - International Society for Experimental Hematology</rights><rights>Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-75e7e2c0a6b6bb9076e568f72b724e88cee683e228ce576e6076d7ffc569cc2d3</citedby><cites>FETCH-LOGICAL-c487t-75e7e2c0a6b6bb9076e568f72b724e88cee683e228ce576e6076d7ffc569cc2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25462021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Folkerts, Hendrik</creatorcontrib><creatorcontrib>Hazenberg, Carin L.E</creatorcontrib><creatorcontrib>Houwerzijl, Ewout J</creatorcontrib><creatorcontrib>van den Heuvel, Fiona A.J</creatorcontrib><creatorcontrib>Mulder, André B</creatorcontrib><creatorcontrib>van der Want, Johannes J.L</creatorcontrib><creatorcontrib>Vellenga, Edo</creatorcontrib><title>Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival</title><title>Experimental hematology</title><addtitle>Exp Hematol</addtitle><description>To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (<3%) based on ultrastructural characteristics and immunogold labeling for activated caspase-3. After 24 h in culture, myelodysplastic erythroblasts exhibited a significant increase in apoptosis (22 ± 7% vs. 3 ± 2%, p = 0.001). In contrast, the myelodysplastic erythroblasts from the hematon fraction did not exhibit an increased tendency toward apoptosis after culture (7 ± 3.3% vs. 1.8 ± 2.3%), which was in line with results for normal bone marrow cells. The same dependency on the micro-environment was noted for immature erythroid progenitor cells. Myelodysplastic hematons exhibited distinct numbers of erythroid burst-forming units in association with an extensive network of stromal cells, whereas small numbers of erythroid burst-forming units were generated from the myelodysplastic mononuclear cells compared with normal mononuclear cells (10.2 ± 9 vs. 162 ± 125, p < 0.001). Co-culture of erythroid myelodysplastic cells in the presence of growth factors (vascular endothelial growth factor, leukemia inhibitory factor) or on the MS-5 stromal layer did not restore the expansion of erythroid precursor cells. These data indicate that surviving myelodysplastic erythroid progenitors become more vulnerable to programmed cell death when they are detached from their own micro-environment.</description><subject>Advanced Basic Science</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Erythroid Precursor Cells - pathology</subject><subject>Erythroid Precursor Cells - physiology</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myelodysplastic Syndromes - physiopathology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Risk Factors</subject><subject>Tumor Microenvironment</subject><issn>0301-472X</issn><issn>1873-2399</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFks9u1DAQxi0EokvhDRDykUuC7SR2ckFCVfkjVeIASNysrD3pepvYweNsyWPwxjjawoELJ1vy75vxfN8Q8pKzkjMu3xxL-DkfYCoF43XJeclY84jseKuqQlRd95jsWMV4USvx_YI8QzyyTDQde0ouRFNLwQTfkV_XcU2HGJylcwy34F0KEekQw0TnPjnwCem9Swc6hvsiOryj0wpjsCvOY4_JGYqrtxkHpH0EamEGb7OMBk_TASguMYbFW-dv6eRMDBT8ycXgpw0aQtwoFzfu5E79-Jw8GfoR4cXDeUm-vb_-evWxuPn84dPVu5vC1K1KhWpAgTCsl3u533dMSWhkOyixV6KGtjUAsq1AiHxr8qPMhFXDYBrZGSNsdUlen-vmuX8sgElPDg2MY-8hLKi5lE3d1VJVGa3PaP49YoRBz9FNfVw1Z3oLQx_1OQy9haE519nqLHv10GHZT2D_iv64n4G3ZwDynCcHUaPJjhuwLoJJ2gb3vw7_FjCj88704x2sgMewRJ891Fyj0Ex_2RZi2wdeM6ZUJ6vfm9W3Mw</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Folkerts, Hendrik</creator><creator>Hazenberg, Carin L.E</creator><creator>Houwerzijl, Ewout J</creator><creator>van den Heuvel, Fiona A.J</creator><creator>Mulder, André B</creator><creator>van der Want, Johannes J.L</creator><creator>Vellenga, Edo</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150301</creationdate><title>Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival</title><author>Folkerts, Hendrik ; Hazenberg, Carin L.E ; Houwerzijl, Ewout J ; van den Heuvel, Fiona A.J ; Mulder, André B ; van der Want, Johannes J.L ; Vellenga, Edo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-75e7e2c0a6b6bb9076e568f72b724e88cee683e228ce576e6076d7ffc569cc2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Advanced Basic Science</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Erythroid Precursor Cells - pathology</topic><topic>Erythroid Precursor Cells - physiology</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myelodysplastic Syndromes - physiopathology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Risk Factors</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Folkerts, Hendrik</creatorcontrib><creatorcontrib>Hazenberg, Carin L.E</creatorcontrib><creatorcontrib>Houwerzijl, Ewout J</creatorcontrib><creatorcontrib>van den Heuvel, Fiona A.J</creatorcontrib><creatorcontrib>Mulder, André B</creatorcontrib><creatorcontrib>van der Want, Johannes J.L</creatorcontrib><creatorcontrib>Vellenga, Edo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Folkerts, Hendrik</au><au>Hazenberg, Carin L.E</au><au>Houwerzijl, Ewout J</au><au>van den Heuvel, Fiona A.J</au><au>Mulder, André B</au><au>van der Want, Johannes J.L</au><au>Vellenga, Edo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival</atitle><jtitle>Experimental hematology</jtitle><addtitle>Exp Hematol</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>43</volume><issue>3</issue><spage>215</spage><epage>222.e2</epage><pages>215-222.e2</pages><issn>0301-472X</issn><eissn>1873-2399</eissn><abstract>To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (<3%) based on ultrastructural characteristics and immunogold labeling for activated caspase-3. After 24 h in culture, myelodysplastic erythroblasts exhibited a significant increase in apoptosis (22 ± 7% vs. 3 ± 2%, p = 0.001). In contrast, the myelodysplastic erythroblasts from the hematon fraction did not exhibit an increased tendency toward apoptosis after culture (7 ± 3.3% vs. 1.8 ± 2.3%), which was in line with results for normal bone marrow cells. The same dependency on the micro-environment was noted for immature erythroid progenitor cells. Myelodysplastic hematons exhibited distinct numbers of erythroid burst-forming units in association with an extensive network of stromal cells, whereas small numbers of erythroid burst-forming units were generated from the myelodysplastic mononuclear cells compared with normal mononuclear cells (10.2 ± 9 vs. 162 ± 125, p < 0.001). Co-culture of erythroid myelodysplastic cells in the presence of growth factors (vascular endothelial growth factor, leukemia inhibitory factor) or on the MS-5 stromal layer did not restore the expansion of erythroid precursor cells. These data indicate that surviving myelodysplastic erythroid progenitors become more vulnerable to programmed cell death when they are detached from their own micro-environment.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>25462021</pmid><doi>10.1016/j.exphem.2014.11.005</doi></addata></record> |
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| identifier | ISSN: 0301-472X |
| ispartof | Experimental hematology, 2015-03, Vol.43 (3), p.215-222.e2 |
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| language | eng |
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| source | ScienceDirect Journals |
| subjects | Advanced Basic Science Aged Aged, 80 and over Apoptosis Cell Survival Cells, Cultured Erythroid Precursor Cells - pathology Erythroid Precursor Cells - physiology Female Flow Cytometry Hematology, Oncology and Palliative Medicine Humans Leukocytes, Mononuclear - pathology Male Middle Aged Myelodysplastic Syndromes - physiopathology Real-Time Polymerase Chain Reaction Risk Factors Tumor Microenvironment |
| title | Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival |
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