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
Hauptverfasser: Cottliar, Alejandra, Pedrazzini, Estela, Corrado, Claudia, Engelberger, María Inés, Narbaitz, Marina, Slavutsky, Irma
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container_end_page 340
container_issue 5
container_start_page 334
container_title European journal of haematology
container_volume 71
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 
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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 &lt; 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P &lt; 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 &lt; 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 &lt; 0.001). Conclusions: MM patients showed a significant reduction in TL (&gt;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. 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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 &lt; 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P &lt; 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 &lt; 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 &lt; 0.001). Conclusions: MM patients showed a significant reduction in TL (&gt;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 &lt; 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P &lt; 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 &lt; 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 &lt; 0.001). Conclusions: MM patients showed a significant reduction in TL (&gt;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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