Telomere shortening in patients with plasma cell disorders
: Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined...
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Veröffentlicht in: | European journal of haematology 2003-11, Vol.71 (5), p.334-340 |
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creator | Cottliar, Alejandra Pedrazzini, Estela Corrado, Claudia Engelberger, María Inés Narbaitz, Marina Slavutsky, Irma |
description | : Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
Methods: Thirty‐one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
Results: TRF analysis in total MM patients showed a mean TRF peak value (5.20 ± 0.35 kb) shorter than those observed in controls (8.5 ± 0.5 kb) (P |
doi_str_mv | 10.1034/j.1600-0609.2003.00157.x |
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Methods: Thirty‐one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
Results: TRF analysis in total MM patients showed a mean TRF peak value (5.20 ± 0.35 kb) shorter than those observed in controls (8.5 ± 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = −0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 ± 1.98%) with respect to MGUS (6.12 ± 1.87%) and normal BM cells (2.00 ± 0.93%) (P < 0.001).
Conclusions: MM patients showed a significant reduction in TL (>60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.</description><identifier>ISSN: 0902-4441</identifier><identifier>EISSN: 1600-0609</identifier><identifier>DOI: 10.1034/j.1600-0609.2003.00157.x</identifier><identifier>PMID: 14667196</identifier><identifier>CODEN: EJHAEC</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Bone Marrow - pathology ; Chromosome Aberrations ; Disease Progression ; Female ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Medical sciences ; monoclonal gammopathy of undetermined significance ; multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - pathology ; Paraproteinemias - genetics ; Paraproteinemias - pathology ; Plasma Cells - pathology ; telomere ; Telomere - ultrastructure ; telomere shortening ; telomeric associations ; terminal restriction fragments</subject><ispartof>European journal of haematology, 2003-11, Vol.71 (5), p.334-340</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4827-605c97b2c675c5a2c21aa8a62fe39ac8c6a3831e8b66c472c5430d550171382b3</citedby><cites>FETCH-LOGICAL-c4827-605c97b2c675c5a2c21aa8a62fe39ac8c6a3831e8b66c472c5430d550171382b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1034%2Fj.1600-0609.2003.00157.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1034%2Fj.1600-0609.2003.00157.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15193165$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14667196$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cottliar, Alejandra</creatorcontrib><creatorcontrib>Pedrazzini, Estela</creatorcontrib><creatorcontrib>Corrado, Claudia</creatorcontrib><creatorcontrib>Engelberger, María Inés</creatorcontrib><creatorcontrib>Narbaitz, Marina</creatorcontrib><creatorcontrib>Slavutsky, Irma</creatorcontrib><title>Telomere shortening in patients with plasma cell disorders</title><title>European journal of haematology</title><addtitle>Eur J Haematol</addtitle><description>: Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
Methods: Thirty‐one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
Results: TRF analysis in total MM patients showed a mean TRF peak value (5.20 ± 0.35 kb) shorter than those observed in controls (8.5 ± 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = −0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 ± 1.98%) with respect to MGUS (6.12 ± 1.87%) and normal BM cells (2.00 ± 0.93%) (P < 0.001).
Conclusions: MM patients showed a significant reduction in TL (>60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.</description><subject>Biological and medical sciences</subject><subject>Bone Marrow - pathology</subject><subject>Chromosome Aberrations</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Karyotyping</subject><subject>Male</subject><subject>Medical sciences</subject><subject>monoclonal gammopathy of undetermined significance</subject><subject>multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - pathology</subject><subject>Paraproteinemias - genetics</subject><subject>Paraproteinemias - pathology</subject><subject>Plasma Cells - pathology</subject><subject>telomere</subject><subject>Telomere - ultrastructure</subject><subject>telomere shortening</subject><subject>telomeric associations</subject><subject>terminal restriction fragments</subject><issn>0902-4441</issn><issn>1600-0609</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMlOwzAUAC0EgrL8AsoFbgnPe4K4IJYWhIBDEdwsx3HBJUuxU9H-PQmtypWTn-QZ-2kQijAkGCg7myZYAMQgIEsIAE0AMJfJYgsNNhfbaAAZkJgxhvfQfghTACAZlrtoDzMhJM7EAJ2PbdlU1tsofDS-tbWr3yNXRzPdOlu3Ifp27Uc0K3WodGRsWUaFC40vrA-HaGeiy2CP1ucBerm9GV-N4oen4d3V5UNsWEpkLICbTObECMkN18QQrHWqBZlYmmmTGqFpSrFNcyEMk8RwRqHgHLDENCU5PUCnq3dnvvma29CqyoV-FV3bZh6UxIxLlpEOTFeg8U0I3k7UzLtK-6XCoPpuaqr6PKrPo_pu6rebWnTq8fqPeV7Z4k9ch-qAkzWgg9HlxOvauPDHcZxRLHjHXay4b1fa5b8XUDf3o27o9Hilu9DaxUbX_lMJSSVXr49DNSJvz5JeXytBfwDkXJYT</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Cottliar, Alejandra</creator><creator>Pedrazzini, Estela</creator><creator>Corrado, Claudia</creator><creator>Engelberger, María Inés</creator><creator>Narbaitz, Marina</creator><creator>Slavutsky, Irma</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><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>200311</creationdate><title>Telomere shortening in patients with plasma cell disorders</title><author>Cottliar, Alejandra ; Pedrazzini, Estela ; Corrado, Claudia ; Engelberger, María Inés ; Narbaitz, Marina ; Slavutsky, Irma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4827-605c97b2c675c5a2c21aa8a62fe39ac8c6a3831e8b66c472c5430d550171382b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Biological and medical sciences</topic><topic>Bone Marrow - pathology</topic><topic>Chromosome Aberrations</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Karyotyping</topic><topic>Male</topic><topic>Medical sciences</topic><topic>monoclonal gammopathy of undetermined significance</topic><topic>multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - pathology</topic><topic>Paraproteinemias - genetics</topic><topic>Paraproteinemias - pathology</topic><topic>Plasma Cells - pathology</topic><topic>telomere</topic><topic>Telomere - ultrastructure</topic><topic>telomere shortening</topic><topic>telomeric associations</topic><topic>terminal restriction fragments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cottliar, Alejandra</creatorcontrib><creatorcontrib>Pedrazzini, Estela</creatorcontrib><creatorcontrib>Corrado, Claudia</creatorcontrib><creatorcontrib>Engelberger, María Inés</creatorcontrib><creatorcontrib>Narbaitz, Marina</creatorcontrib><creatorcontrib>Slavutsky, Irma</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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>European journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cottliar, Alejandra</au><au>Pedrazzini, Estela</au><au>Corrado, Claudia</au><au>Engelberger, María Inés</au><au>Narbaitz, Marina</au><au>Slavutsky, Irma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomere shortening in patients with plasma cell disorders</atitle><jtitle>European journal of haematology</jtitle><addtitle>Eur J Haematol</addtitle><date>2003-11</date><risdate>2003</risdate><volume>71</volume><issue>5</issue><spage>334</spage><epage>340</epage><pages>334-340</pages><issn>0902-4441</issn><eissn>1600-0609</eissn><coden>EJHAEC</coden><abstract>: Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
Methods: Thirty‐one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.
Results: TRF analysis in total MM patients showed a mean TRF peak value (5.20 ± 0.35 kb) shorter than those observed in controls (8.5 ± 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = −0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 ± 1.98%) with respect to MGUS (6.12 ± 1.87%) and normal BM cells (2.00 ± 0.93%) (P < 0.001).
Conclusions: MM patients showed a significant reduction in TL (>60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>14667196</pmid><doi>10.1034/j.1600-0609.2003.00157.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biological and medical sciences Bone Marrow - pathology Chromosome Aberrations Disease Progression Female Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology In Situ Hybridization, Fluorescence Karyotyping Male Medical sciences monoclonal gammopathy of undetermined significance multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - pathology Paraproteinemias - genetics Paraproteinemias - pathology Plasma Cells - pathology telomere Telomere - ultrastructure telomere shortening telomeric associations terminal restriction fragments |
title | Telomere shortening in patients with plasma cell disorders |
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