Early Suppressive Effects of Chemotherapy on Recovery of Bone Marrow Megakaryocyte Precursors: Possible Relationship to Platelet Recovery
This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5‐fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 1996, Vol.14 (S1), p.31-37 |
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| creator | Warren, M. Kim Zujewski, Joanne Rose, Wendy L. Szabo, Janet M. O'Shaughnessy, Joyce A. Halverson, David C. Cowan, Kenneth H. Gress, Ronald E. Schwartz, Gretchen N. |
| description | This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5‐fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme‐linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre‐chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post‐chemotherapy CD34+ cells from four patients were similar to values from pre‐chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post‐chemotherapy CD34+ cells from two other patients were low (absorbance |
| doi_str_mv | 10.1002/stem.5530140704 |
| format | Article |
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Kim ; Zujewski, Joanne ; Rose, Wendy L. ; Szabo, Janet M. ; O'Shaughnessy, Joyce A. ; Halverson, David C. ; Cowan, Kenneth H. ; Gress, Ronald E. ; Schwartz, Gretchen N.</creator><creatorcontrib>Warren, M. Kim ; Zujewski, Joanne ; Rose, Wendy L. ; Szabo, Janet M. ; O'Shaughnessy, Joyce A. ; Halverson, David C. ; Cowan, Kenneth H. ; Gress, Ronald E. ; Schwartz, Gretchen N.</creatorcontrib><description>This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5‐fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme‐linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre‐chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post‐chemotherapy CD34+ cells from four patients were similar to values from pre‐chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post‐chemotherapy CD34+ cells from two other patients were low (absorbance <0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/μI during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post‐chemotherapy CD34+ cells had absorbance values ≥ 1.0 developed platelet nadirs less than 20,000/μl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.5530140704</identifier><identifier>PMID: 11012200</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Antigens, CD34 - biosynthesis ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Blood Cell Count ; Blood Platelets - drug effects ; Bone Marrow Cells - drug effects ; Breast Neoplasms - drug therapy ; Case-Control Studies ; CD34+ cells ; Chemotherapy ; Cyclophosphamide - therapeutic use ; Doxorubicin - therapeutic use ; ELISA ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorouracil - therapeutic use ; Glycoprotein GPIIb/IIIa ; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology ; Humans ; Interleukin-3 - metabolism ; Interleukin-3 - pharmacology ; Leucovorin - therapeutic use ; Megakaryocytes ; Megakaryocytes - metabolism ; Megakaryocytes - physiology ; Platelet Glycoprotein GPIIb-IIIa Complex - biosynthesis ; Recombinant Fusion Proteins - pharmacology ; Stem Cell Factor - metabolism ; Thrombocytopenia - etiology ; Time Factors</subject><ispartof>Stem cells (Dayton, Ohio), 1996, Vol.14 (S1), p.31-37</ispartof><rights>Copyright © 1996 AlphaMed Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2604-28e14e8fd96adea773af8290a195dd28646caeda128614c4ae9e55a01496ef4b3</citedby><cites>FETCH-LOGICAL-c2604-28e14e8fd96adea773af8290a195dd28646caeda128614c4ae9e55a01496ef4b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11012200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Warren, M. Kim</creatorcontrib><creatorcontrib>Zujewski, Joanne</creatorcontrib><creatorcontrib>Rose, Wendy L.</creatorcontrib><creatorcontrib>Szabo, Janet M.</creatorcontrib><creatorcontrib>O'Shaughnessy, Joyce A.</creatorcontrib><creatorcontrib>Halverson, David C.</creatorcontrib><creatorcontrib>Cowan, Kenneth H.</creatorcontrib><creatorcontrib>Gress, Ronald E.</creatorcontrib><creatorcontrib>Schwartz, Gretchen N.</creatorcontrib><title>Early Suppressive Effects of Chemotherapy on Recovery of Bone Marrow Megakaryocyte Precursors: Possible Relationship to Platelet Recovery</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5‐fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme‐linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre‐chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post‐chemotherapy CD34+ cells from four patients were similar to values from pre‐chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post‐chemotherapy CD34+ cells from two other patients were low (absorbance <0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/μI during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post‐chemotherapy CD34+ cells had absorbance values ≥ 1.0 developed platelet nadirs less than 20,000/μl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.</description><subject>Antigens, CD34 - biosynthesis</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Blood Cell Count</subject><subject>Blood Platelets - drug effects</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Case-Control Studies</subject><subject>CD34+ cells</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Doxorubicin - therapeutic use</subject><subject>ELISA</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Fluorouracil - therapeutic use</subject><subject>Glycoprotein GPIIb/IIIa</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</subject><subject>Humans</subject><subject>Interleukin-3 - metabolism</subject><subject>Interleukin-3 - pharmacology</subject><subject>Leucovorin - therapeutic use</subject><subject>Megakaryocytes</subject><subject>Megakaryocytes - metabolism</subject><subject>Megakaryocytes - physiology</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - biosynthesis</subject><subject>Recombinant Fusion Proteins - pharmacology</subject><subject>Stem Cell Factor - metabolism</subject><subject>Thrombocytopenia - etiology</subject><subject>Time Factors</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkN9OwjAUxhujEUSvvTN9gUE72rHqlS7zTwKRCF4vpTuV6UaXdkD2CL61JRDxzqtzTs73_XLOh9A1JX1KSDhwDVR9zoeEMjIi7AR1KWciYILGp74nURRwIkQHXTj3SbyKx_E56lBKaBgS0kXfqbRli2frurbgXLEBnGoNqnHYaJwsoTLNEqysW2xW-A2U2YBtd7sHswI8kdaaLZ7Ah_yStjWqbQBPLai1dca6Wzw1HroowVtL2RRm5ZZFjRuDp36EEppf5iU607J0cHWoPfT-mM6T52D8-vSS3I8DFUaEBWEMlEGscxHJHORoNJQ6DgWRVPA8D-OIRUpCLqlvKVNMggDOpX9dRKDZYthDgz1XWX-bBZ3Vtqj88Rkl2S7UbBdqdgzVO272jnq9qCA_6g8pesHdXrAtSmj_42WzeTr5g_8BWUuH9Q</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>Warren, M. Kim</creator><creator>Zujewski, Joanne</creator><creator>Rose, Wendy L.</creator><creator>Szabo, Janet M.</creator><creator>O'Shaughnessy, Joyce A.</creator><creator>Halverson, David C.</creator><creator>Cowan, Kenneth H.</creator><creator>Gress, Ronald E.</creator><creator>Schwartz, Gretchen N.</creator><general>John Wiley & Sons, Ltd</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></search><sort><creationdate>1996</creationdate><title>Early Suppressive Effects of Chemotherapy on Recovery of Bone Marrow Megakaryocyte Precursors: Possible Relationship to Platelet Recovery</title><author>Warren, M. Kim ; Zujewski, Joanne ; Rose, Wendy L. ; Szabo, Janet M. ; O'Shaughnessy, Joyce A. ; Halverson, David C. ; Cowan, Kenneth H. ; Gress, Ronald E. ; Schwartz, Gretchen N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2604-28e14e8fd96adea773af8290a195dd28646caeda128614c4ae9e55a01496ef4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Antigens, CD34 - biosynthesis</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Blood Cell Count</topic><topic>Blood Platelets - drug effects</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Case-Control Studies</topic><topic>CD34+ cells</topic><topic>Chemotherapy</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Doxorubicin - therapeutic use</topic><topic>ELISA</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Fluorouracil - therapeutic use</topic><topic>Glycoprotein GPIIb/IIIa</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</topic><topic>Humans</topic><topic>Interleukin-3 - metabolism</topic><topic>Interleukin-3 - pharmacology</topic><topic>Leucovorin - therapeutic use</topic><topic>Megakaryocytes</topic><topic>Megakaryocytes - metabolism</topic><topic>Megakaryocytes - physiology</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - biosynthesis</topic><topic>Recombinant Fusion Proteins - pharmacology</topic><topic>Stem Cell Factor - metabolism</topic><topic>Thrombocytopenia - etiology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Warren, M. Kim</creatorcontrib><creatorcontrib>Zujewski, Joanne</creatorcontrib><creatorcontrib>Rose, Wendy L.</creatorcontrib><creatorcontrib>Szabo, Janet M.</creatorcontrib><creatorcontrib>O'Shaughnessy, Joyce A.</creatorcontrib><creatorcontrib>Halverson, David C.</creatorcontrib><creatorcontrib>Cowan, Kenneth H.</creatorcontrib><creatorcontrib>Gress, Ronald E.</creatorcontrib><creatorcontrib>Schwartz, Gretchen N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Warren, M. Kim</au><au>Zujewski, Joanne</au><au>Rose, Wendy L.</au><au>Szabo, Janet M.</au><au>O'Shaughnessy, Joyce A.</au><au>Halverson, David C.</au><au>Cowan, Kenneth H.</au><au>Gress, Ronald E.</au><au>Schwartz, Gretchen N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early Suppressive Effects of Chemotherapy on Recovery of Bone Marrow Megakaryocyte Precursors: Possible Relationship to Platelet Recovery</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>1996</date><risdate>1996</risdate><volume>14</volume><issue>S1</issue><spage>31</spage><epage>37</epage><pages>31-37</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>This study utilized a recently developed culture and quantitation system to detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and breast cancer patients treated with 5‐fluorouracil, leucovorin, adriamycin and cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells were isolated and placed in liquid culture with growth factors to stimulate proliferation and lineage commitment. Absorbance values from an enzyme‐linked immunosorbent assay were used to quantitate expression of platelet glycoprotein GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells seeded per culture that was associated with an increase in the number of megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance values for expression of GPIIb/IIIa from 2,000 normal donor and pre‐chemotherapy CD34+ marrow cells were ≥ 1.0. Absorbance values from cultures of post‐chemotherapy CD34+ cells from four patients were similar to values from pre‐chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post‐chemotherapy CD34+ cells from two other patients were low (absorbance <0.5). Low absorbance values for GPIIb/IIIa expression indicate that megakaryocyte production from those CD34+ cells was reduced. Both of those patients developed prolonged thrombocytopenia and platelet nadirs of less than 20,000/μI during FLAC chemotherapy. In contrast, only one out of four patients whose cultures of post‐chemotherapy CD34+ cells had absorbance values ≥ 1.0 developed platelet nadirs less than 20,000/μl. These results suggest that low platelet nadirs and delayed platelet recovery may be associated with suppressive effects of chemotherapy on recovery of megakaryocyte precursors.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>11012200</pmid><doi>10.1002/stem.5530140704</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1066-5099 |
| ispartof | Stem cells (Dayton, Ohio), 1996, Vol.14 (S1), p.31-37 |
| issn | 1066-5099 1549-4918 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_stem_5530140704 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antigens, CD34 - biosynthesis Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Blood Cell Count Blood Platelets - drug effects Bone Marrow Cells - drug effects Breast Neoplasms - drug therapy Case-Control Studies CD34+ cells Chemotherapy Cyclophosphamide - therapeutic use Doxorubicin - therapeutic use ELISA Enzyme-Linked Immunosorbent Assay Female Fluorouracil - therapeutic use Glycoprotein GPIIb/IIIa Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Humans Interleukin-3 - metabolism Interleukin-3 - pharmacology Leucovorin - therapeutic use Megakaryocytes Megakaryocytes - metabolism Megakaryocytes - physiology Platelet Glycoprotein GPIIb-IIIa Complex - biosynthesis Recombinant Fusion Proteins - pharmacology Stem Cell Factor - metabolism Thrombocytopenia - etiology Time Factors |
| title | Early Suppressive Effects of Chemotherapy on Recovery of Bone Marrow Megakaryocyte Precursors: Possible Relationship to Platelet Recovery |
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