Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent
Background Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expre...
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| Veröffentlicht in: | Cytometry. Part B, Clinical cytometry Clinical cytometry, 2022-11, Vol.102 (6), p.462-470 |
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| creator | Sriram, Harshini Kunjachan, Florence Khanka, Twinkle Gawai, Sangamitra Ghogale, Sitaram Deshpande, Nilesh Girase, Karishma Patil, Jagruti Chatterjee, Gaurav Rajpal, Sweta Patkar, Nikhil V. Bagal, Bhausaheb Jain, Hasmukh Sengar, Manju Hasan, Syed Khizer Khattry, Navin Subramanian, Papagudi G. Gujral, Sumeet Tembhare, Prashant R. |
| description | Background
Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients.
Methods
We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF).
Results
Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p |
| doi_str_mv | 10.1002/cyto.b.22099 |
| format | Article |
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Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients.
Methods
We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF).
Results
Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529.
Conclusions
We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.</description><identifier>ISSN: 1552-4949</identifier><identifier>EISSN: 1552-4957</identifier><identifier>DOI: 10.1002/cyto.b.22099</identifier><identifier>PMID: 36346307</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Antibodies ; Antigen-presenting cells ; Antigens ; B-Cell Maturation Antigen - metabolism ; Bone marrow ; CD269 ; Cell surface ; Coefficient of variation ; Diagnosis ; Female ; Flow Cytometry ; Fluorescence ; Humans ; Immunofluorescence ; Immunotherapy ; Immunotherapy, Adoptive ; Lymphocytes ; Lymphocytes T ; Male ; Maturation ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - metabolism ; Neoplasm Recurrence, Local ; Patients ; Plasma cells ; Protein B ; targeted therapy</subject><ispartof>Cytometry. Part B, Clinical cytometry, 2022-11, Vol.102 (6), p.462-470</ispartof><rights>2022 International Clinical Cytometry Society.</rights><rights>2022 International Clinical Cytometry Society</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3649-94cdb6d80c1ffc76393a64157a76fa83e8c8bde80965e7da16eea7670257b6773</citedby><cites>FETCH-LOGICAL-c3649-94cdb6d80c1ffc76393a64157a76fa83e8c8bde80965e7da16eea7670257b6773</cites><orcidid>0000-0002-0161-8668 ; 0000-0002-6505-7898 ; 0000-0002-9030-0415</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcyto.b.22099$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcyto.b.22099$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36346307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sriram, Harshini</creatorcontrib><creatorcontrib>Kunjachan, Florence</creatorcontrib><creatorcontrib>Khanka, Twinkle</creatorcontrib><creatorcontrib>Gawai, Sangamitra</creatorcontrib><creatorcontrib>Ghogale, Sitaram</creatorcontrib><creatorcontrib>Deshpande, Nilesh</creatorcontrib><creatorcontrib>Girase, Karishma</creatorcontrib><creatorcontrib>Patil, Jagruti</creatorcontrib><creatorcontrib>Chatterjee, Gaurav</creatorcontrib><creatorcontrib>Rajpal, Sweta</creatorcontrib><creatorcontrib>Patkar, Nikhil V.</creatorcontrib><creatorcontrib>Bagal, Bhausaheb</creatorcontrib><creatorcontrib>Jain, Hasmukh</creatorcontrib><creatorcontrib>Sengar, Manju</creatorcontrib><creatorcontrib>Hasan, Syed Khizer</creatorcontrib><creatorcontrib>Khattry, Navin</creatorcontrib><creatorcontrib>Subramanian, Papagudi G.</creatorcontrib><creatorcontrib>Gujral, Sumeet</creatorcontrib><creatorcontrib>Tembhare, Prashant R.</creatorcontrib><title>Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent</title><title>Cytometry. Part B, Clinical cytometry</title><addtitle>Cytometry B Clin Cytom</addtitle><description>Background
Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients.
Methods
We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF).
Results
Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529.
Conclusions
We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Antigen-presenting cells</subject><subject>Antigens</subject><subject>B-Cell Maturation Antigen - metabolism</subject><subject>Bone marrow</subject><subject>CD269</subject><subject>Cell surface</subject><subject>Coefficient of variation</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorescence</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunotherapy</subject><subject>Immunotherapy, Adoptive</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Maturation</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - metabolism</subject><subject>Neoplasm Recurrence, Local</subject><subject>Patients</subject><subject>Plasma cells</subject><subject>Protein B</subject><subject>targeted therapy</subject><issn>1552-4949</issn><issn>1552-4957</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kbFu1TAUhi0EoqWwMSNLLB24Fzt27GSkVwUqVerSDp0sxzmpXDl2sB1Ktj5Cn5EnwektHRiQh2PrfOeTj36E3lOypYRUn82Sw7bbVhVp2xfokNZ1teFtLV8-33l7gN6kdEsIq7mQr9EBE4wLRuQhejj9NUVIyQaPHfwEl7D2PZ50zhB9wmHAJ7_vHww4h0ed56jzimqf7Q14bD32cOcW3Ft940OC_nE8gtPT-hhnl-3kAI8LuDDqVWzB54SHGEZ85sucx2nuTChGXzpv0atBuwTvnuoRuvp6ern7vjm_-Ha2-3K-MUzwdtNy03eib4ihw2CkYC3TgtNaaikG3TBoTNP10JBW1CB7TQVAaUlS1bITUrIjdLz3TjH8mCFlNdq0rqk9hDmpSjJOhWypKOjHf9DbMEdffrdS5XBes0J92lMmhpQiDGqKdtRxUZSoNSm1JqU69ZhUwT88SeduhP4Z_htNAfgeuLMOlv_K1O768uJk7_0DJJij8g</recordid><startdate>202211</startdate><enddate>202211</enddate><creator>Sriram, Harshini</creator><creator>Kunjachan, Florence</creator><creator>Khanka, Twinkle</creator><creator>Gawai, Sangamitra</creator><creator>Ghogale, Sitaram</creator><creator>Deshpande, Nilesh</creator><creator>Girase, Karishma</creator><creator>Patil, Jagruti</creator><creator>Chatterjee, Gaurav</creator><creator>Rajpal, Sweta</creator><creator>Patkar, Nikhil V.</creator><creator>Bagal, Bhausaheb</creator><creator>Jain, Hasmukh</creator><creator>Sengar, Manju</creator><creator>Hasan, Syed Khizer</creator><creator>Khattry, Navin</creator><creator>Subramanian, Papagudi G.</creator><creator>Gujral, Sumeet</creator><creator>Tembhare, Prashant R.</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, 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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0161-8668</orcidid><orcidid>https://orcid.org/0000-0002-6505-7898</orcidid><orcidid>https://orcid.org/0000-0002-9030-0415</orcidid></search><sort><creationdate>202211</creationdate><title>Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent</title><author>Sriram, Harshini ; Kunjachan, Florence ; Khanka, Twinkle ; Gawai, Sangamitra ; Ghogale, Sitaram ; Deshpande, Nilesh ; Girase, Karishma ; Patil, Jagruti ; Chatterjee, Gaurav ; Rajpal, Sweta ; Patkar, Nikhil V. ; Bagal, Bhausaheb ; Jain, Hasmukh ; Sengar, Manju ; Hasan, Syed Khizer ; Khattry, Navin ; Subramanian, Papagudi G. ; Gujral, Sumeet ; Tembhare, Prashant R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3649-94cdb6d80c1ffc76393a64157a76fa83e8c8bde80965e7da16eea7670257b6773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Antigen-presenting cells</topic><topic>Antigens</topic><topic>B-Cell Maturation Antigen - metabolism</topic><topic>Bone marrow</topic><topic>CD269</topic><topic>Cell surface</topic><topic>Coefficient of variation</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fluorescence</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunotherapy</topic><topic>Immunotherapy, Adoptive</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Maturation</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - metabolism</topic><topic>Neoplasm Recurrence, Local</topic><topic>Patients</topic><topic>Plasma cells</topic><topic>Protein B</topic><topic>targeted therapy</topic><toplevel>online_resources</toplevel><creatorcontrib>Sriram, Harshini</creatorcontrib><creatorcontrib>Kunjachan, Florence</creatorcontrib><creatorcontrib>Khanka, Twinkle</creatorcontrib><creatorcontrib>Gawai, Sangamitra</creatorcontrib><creatorcontrib>Ghogale, Sitaram</creatorcontrib><creatorcontrib>Deshpande, Nilesh</creatorcontrib><creatorcontrib>Girase, Karishma</creatorcontrib><creatorcontrib>Patil, Jagruti</creatorcontrib><creatorcontrib>Chatterjee, Gaurav</creatorcontrib><creatorcontrib>Rajpal, Sweta</creatorcontrib><creatorcontrib>Patkar, Nikhil V.</creatorcontrib><creatorcontrib>Bagal, Bhausaheb</creatorcontrib><creatorcontrib>Jain, Hasmukh</creatorcontrib><creatorcontrib>Sengar, Manju</creatorcontrib><creatorcontrib>Hasan, Syed Khizer</creatorcontrib><creatorcontrib>Khattry, Navin</creatorcontrib><creatorcontrib>Subramanian, Papagudi G.</creatorcontrib><creatorcontrib>Gujral, Sumeet</creatorcontrib><creatorcontrib>Tembhare, Prashant R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cytometry. Part B, Clinical cytometry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sriram, Harshini</au><au>Kunjachan, Florence</au><au>Khanka, Twinkle</au><au>Gawai, Sangamitra</au><au>Ghogale, Sitaram</au><au>Deshpande, Nilesh</au><au>Girase, Karishma</au><au>Patil, Jagruti</au><au>Chatterjee, Gaurav</au><au>Rajpal, Sweta</au><au>Patkar, Nikhil V.</au><au>Bagal, Bhausaheb</au><au>Jain, Hasmukh</au><au>Sengar, Manju</au><au>Hasan, Syed Khizer</au><au>Khattry, Navin</au><au>Subramanian, Papagudi G.</au><au>Gujral, Sumeet</au><au>Tembhare, Prashant R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent</atitle><jtitle>Cytometry. Part B, Clinical cytometry</jtitle><addtitle>Cytometry B Clin Cytom</addtitle><date>2022-11</date><risdate>2022</risdate><volume>102</volume><issue>6</issue><spage>462</spage><epage>470</epage><pages>462-470</pages><issn>1552-4949</issn><eissn>1552-4957</eissn><abstract>Background
Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients.
Methods
We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF).
Results
Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529.
Conclusions
We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>36346307</pmid><doi>10.1002/cyto.b.22099</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0161-8668</orcidid><orcidid>https://orcid.org/0000-0002-6505-7898</orcidid><orcidid>https://orcid.org/0000-0002-9030-0415</orcidid></addata></record> |
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| ispartof | Cytometry. Part B, Clinical cytometry, 2022-11, Vol.102 (6), p.462-470 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antibodies Antigen-presenting cells Antigens B-Cell Maturation Antigen - metabolism Bone marrow CD269 Cell surface Coefficient of variation Diagnosis Female Flow Cytometry Fluorescence Humans Immunofluorescence Immunotherapy Immunotherapy, Adoptive Lymphocytes Lymphocytes T Male Maturation Middle Aged Multiple myeloma Multiple Myeloma - metabolism Neoplasm Recurrence, Local Patients Plasma cells Protein B targeted therapy |
| title | Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent |
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