MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio
This study investigates the intertwined processes of (anti-)apoptosis and cell proliferation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Utilizing antibodies to Bcl-2 and Ki-67, the CD34-positive blast cell compartments in bone marrow aspirates from 50 non-malignant cases, 2...
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| Veröffentlicht in: | Leukemia research 2024-07, Vol.142, p.107520, Article 107520 |
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| creator | Mestrum, Stefan G.C. Roanalis, B.Y. Vanblarcum de Wit, Norbert C.J. Drent, Roosmarie J.M. Boonen, Bert T. van Hemert, Wouter L.W. Hopman, Anton H.N. Ramaekers, Frans C.S. Leers, Math P.G. |
| description | This study investigates the intertwined processes of (anti-)apoptosis and cell proliferation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Utilizing antibodies to Bcl-2 and Ki-67, the CD34-positive blast cell compartments in bone marrow aspirates from 50 non-malignant cases, 25 MDS patients, and 25 AML patients were analyzed for their anti-apoptotic and proliferative cell fractions through ten-color flow cytometry. MDS patients exhibited a significantly increased anti-apoptotic (p=0.0014) and reduced proliferative cell fraction (p=0.0030) in their blast cell population as compared to non-malignant cases. AML patients showed an even more exacerbated trend than MDS patients. The resulting Bcl-2:Ki-67 cell fraction ratios in MDS and AML were significantly increased as compared to the non-malignant cases (p=0.0004 and p |
| doi_str_mv | 10.1016/j.leukres.2024.107520 |
| format | Article |
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Integrating these two dynamic markers into MDS and AML diagnostic workups may enable informed conclusions about their biological behavior, facilitating individualized therapy decisions for patients.
•Anti-apoptotic (Bcl-2 positive) blast cell populations increase in MDS/AML.•Proliferative (Ki-67 positive) blast cell populations decrease in MDS/AML.•Bcl-2:Ki-67 fraction ratio increases significantly in MDS/AML blast cell populations.•Bcl-2:Ki-67 fraction ratio may be a predictive marker for progression of MDS to AML.</description><identifier>ISSN: 0145-2126</identifier><identifier>ISSN: 1873-5835</identifier><identifier>EISSN: 1873-5835</identifier><identifier>DOI: 10.1016/j.leukres.2024.107520</identifier><identifier>PMID: 38776565</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; AML ; Anti-apoptosis ; Antigens, CD34 - analysis ; Antigens, CD34 - metabolism ; Apoptosis ; Bcl-2 ; Cell Proliferation ; Female ; Flow Cytometry ; Humans ; Ki-67 ; Ki-67 Antigen - analysis ; Ki-67 Antigen - metabolism ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - pathology ; Male ; MDS ; Middle Aged ; Multiparameter flow cytometry ; Myelodysplastic Syndromes - metabolism ; Myelodysplastic Syndromes - pathology ; Proliferation ; Proto-Oncogene Proteins c-bcl-2 - analysis ; Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><ispartof>Leukemia research, 2024-07, Vol.142, p.107520, Article 107520</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c360t-14a3ba8c9951a28239e5659bef1c7bb88b1feba612025786b583bf3f4a7c4c343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0145212624000869$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38776565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mestrum, Stefan G.C.</creatorcontrib><creatorcontrib>Roanalis, B.Y. Vanblarcum</creatorcontrib><creatorcontrib>de Wit, Norbert C.J.</creatorcontrib><creatorcontrib>Drent, Roosmarie J.M.</creatorcontrib><creatorcontrib>Boonen, Bert T.</creatorcontrib><creatorcontrib>van Hemert, Wouter L.W.</creatorcontrib><creatorcontrib>Hopman, Anton H.N.</creatorcontrib><creatorcontrib>Ramaekers, Frans C.S.</creatorcontrib><creatorcontrib>Leers, Math P.G.</creatorcontrib><title>MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio</title><title>Leukemia research</title><addtitle>Leuk Res</addtitle><description>This study investigates the intertwined processes of (anti-)apoptosis and cell proliferation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Utilizing antibodies to Bcl-2 and Ki-67, the CD34-positive blast cell compartments in bone marrow aspirates from 50 non-malignant cases, 25 MDS patients, and 25 AML patients were analyzed for their anti-apoptotic and proliferative cell fractions through ten-color flow cytometry. MDS patients exhibited a significantly increased anti-apoptotic (p=0.0014) and reduced proliferative cell fraction (p=0.0030) in their blast cell population as compared to non-malignant cases. AML patients showed an even more exacerbated trend than MDS patients. The resulting Bcl-2:Ki-67 cell fraction ratios in MDS and AML were significantly increased as compared to the non-malignant cases (p=0.0004 and p<0.0001, respectively). AML patients displayed, however, a high degree of variability in their anti-apoptotic and proliferation index, attributed to heterogeneity in maturation stage and severity of the disease at diagnosis. Using double-labeling for Bcl-2 and Ki-67 it could be shown that besides blast cells with a mutually exclusive Ki-67 and Bcl-2 expression, also blast cells concurrently exhibiting anti-apoptotic and proliferative marker expression were found.
Integrating these two dynamic markers into MDS and AML diagnostic workups may enable informed conclusions about their biological behavior, facilitating individualized therapy decisions for patients.
•Anti-apoptotic (Bcl-2 positive) blast cell populations increase in MDS/AML.•Proliferative (Ki-67 positive) blast cell populations decrease in MDS/AML.•Bcl-2:Ki-67 fraction ratio increases significantly in MDS/AML blast cell populations.•Bcl-2:Ki-67 fraction ratio may be a predictive marker for progression of MDS to AML.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AML</subject><subject>Anti-apoptosis</subject><subject>Antigens, CD34 - analysis</subject><subject>Antigens, CD34 - metabolism</subject><subject>Apoptosis</subject><subject>Bcl-2</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Ki-67</subject><subject>Ki-67 Antigen - analysis</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Male</subject><subject>MDS</subject><subject>Middle Aged</subject><subject>Multiparameter flow cytometry</subject><subject>Myelodysplastic Syndromes - metabolism</subject><subject>Myelodysplastic Syndromes - pathology</subject><subject>Proliferation</subject><subject>Proto-Oncogene Proteins c-bcl-2 - analysis</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><issn>0145-2126</issn><issn>1873-5835</issn><issn>1873-5835</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtPGzEUha2qqKS0P4HKy24m9WM8jxVCoS8piAXt2rI918TpZDzYniCW_PM6TGDL6ki-59zr8yF0TsmSElp92y57mP4FiEtGWJnfasHIO7SgTc0L0XDxHi0ILUXBKKtO0ccYt4QQ0dL2AzrlTV1XohIL9HR9dYvV0OHL6zWOG_-AoYe9StBhG5RJzg8Re4tXV7wsRh9dcnvAulcxYQN9j0c_Tr2afQ8ubbDCG3eXZUiuUHmafHIG7yHEKeIx-N5ZCM8B_Cyf0IlVfYTPRz1Df398_7P6Vaxvfv5eXa4LwyuSCloqrlVj2lZQxRrGW8gFWg2WmlrrptHUglYVzThE3VQ6M9CW21LVpjS85Gfo67w3_-F-gpjkzsVDBTWAn6LkGQ4TbUlZtorZaoKPMYCVY3A7FR4lJfJAX27lkb480Jcz_Zz7cjwx6R10r6kX3NlwMRsgF907CDIaB4OBzgUwSXbevXHiPytQmhQ</recordid><startdate>202407</startdate><enddate>202407</enddate><creator>Mestrum, Stefan G.C.</creator><creator>Roanalis, B.Y. Vanblarcum</creator><creator>de Wit, Norbert C.J.</creator><creator>Drent, Roosmarie J.M.</creator><creator>Boonen, Bert T.</creator><creator>van Hemert, Wouter L.W.</creator><creator>Hopman, Anton H.N.</creator><creator>Ramaekers, Frans C.S.</creator><creator>Leers, Math P.G.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>202407</creationdate><title>MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio</title><author>Mestrum, Stefan G.C. ; Roanalis, B.Y. Vanblarcum ; de Wit, Norbert C.J. ; Drent, Roosmarie J.M. ; Boonen, Bert T. ; van Hemert, Wouter L.W. ; Hopman, Anton H.N. ; Ramaekers, Frans C.S. ; Leers, Math P.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-14a3ba8c9951a28239e5659bef1c7bb88b1feba612025786b583bf3f4a7c4c343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>AML</topic><topic>Anti-apoptosis</topic><topic>Antigens, CD34 - analysis</topic><topic>Antigens, CD34 - metabolism</topic><topic>Apoptosis</topic><topic>Bcl-2</topic><topic>Cell Proliferation</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Ki-67</topic><topic>Ki-67 Antigen - analysis</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Male</topic><topic>MDS</topic><topic>Middle Aged</topic><topic>Multiparameter flow cytometry</topic><topic>Myelodysplastic Syndromes - metabolism</topic><topic>Myelodysplastic Syndromes - pathology</topic><topic>Proliferation</topic><topic>Proto-Oncogene Proteins c-bcl-2 - analysis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mestrum, Stefan G.C.</creatorcontrib><creatorcontrib>Roanalis, B.Y. Vanblarcum</creatorcontrib><creatorcontrib>de Wit, Norbert C.J.</creatorcontrib><creatorcontrib>Drent, Roosmarie J.M.</creatorcontrib><creatorcontrib>Boonen, Bert T.</creatorcontrib><creatorcontrib>van Hemert, Wouter L.W.</creatorcontrib><creatorcontrib>Hopman, Anton H.N.</creatorcontrib><creatorcontrib>Ramaekers, Frans C.S.</creatorcontrib><creatorcontrib>Leers, Math P.G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Leukemia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mestrum, Stefan G.C.</au><au>Roanalis, B.Y. Vanblarcum</au><au>de Wit, Norbert C.J.</au><au>Drent, Roosmarie J.M.</au><au>Boonen, Bert T.</au><au>van Hemert, Wouter L.W.</au><au>Hopman, Anton H.N.</au><au>Ramaekers, Frans C.S.</au><au>Leers, Math P.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio</atitle><jtitle>Leukemia research</jtitle><addtitle>Leuk Res</addtitle><date>2024-07</date><risdate>2024</risdate><volume>142</volume><spage>107520</spage><pages>107520-</pages><artnum>107520</artnum><issn>0145-2126</issn><issn>1873-5835</issn><eissn>1873-5835</eissn><abstract>This study investigates the intertwined processes of (anti-)apoptosis and cell proliferation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Utilizing antibodies to Bcl-2 and Ki-67, the CD34-positive blast cell compartments in bone marrow aspirates from 50 non-malignant cases, 25 MDS patients, and 25 AML patients were analyzed for their anti-apoptotic and proliferative cell fractions through ten-color flow cytometry. MDS patients exhibited a significantly increased anti-apoptotic (p=0.0014) and reduced proliferative cell fraction (p=0.0030) in their blast cell population as compared to non-malignant cases. AML patients showed an even more exacerbated trend than MDS patients. The resulting Bcl-2:Ki-67 cell fraction ratios in MDS and AML were significantly increased as compared to the non-malignant cases (p=0.0004 and p<0.0001, respectively). AML patients displayed, however, a high degree of variability in their anti-apoptotic and proliferation index, attributed to heterogeneity in maturation stage and severity of the disease at diagnosis. Using double-labeling for Bcl-2 and Ki-67 it could be shown that besides blast cells with a mutually exclusive Ki-67 and Bcl-2 expression, also blast cells concurrently exhibiting anti-apoptotic and proliferative marker expression were found.
Integrating these two dynamic markers into MDS and AML diagnostic workups may enable informed conclusions about their biological behavior, facilitating individualized therapy decisions for patients.
•Anti-apoptotic (Bcl-2 positive) blast cell populations increase in MDS/AML.•Proliferative (Ki-67 positive) blast cell populations decrease in MDS/AML.•Bcl-2:Ki-67 fraction ratio increases significantly in MDS/AML blast cell populations.•Bcl-2:Ki-67 fraction ratio may be a predictive marker for progression of MDS to AML.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38776565</pmid><doi>10.1016/j.leukres.2024.107520</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over AML Anti-apoptosis Antigens, CD34 - analysis Antigens, CD34 - metabolism Apoptosis Bcl-2 Cell Proliferation Female Flow Cytometry Humans Ki-67 Ki-67 Antigen - analysis Ki-67 Antigen - metabolism Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Male MDS Middle Aged Multiparameter flow cytometry Myelodysplastic Syndromes - metabolism Myelodysplastic Syndromes - pathology Proliferation Proto-Oncogene Proteins c-bcl-2 - analysis Proto-Oncogene Proteins c-bcl-2 - metabolism |
| title | MDS and AML show elevated fractions of CD34-positive blast cell populations with a high anti-apoptotic versus proliferation ratio |
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