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Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B‐lineage acute lymphoblastic leukemia

Introduction In this study, we aimed to compare the immunophenotype of tumor cells in children with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the...

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Published in:International journal of laboratory hematology 2023-06, Vol.45 (3), p.337-343
Main Authors: Demina, Irina, Zerkalenkova, Elena, Soldatkina, Olga, Kazakova, Anna, Semchenkova, Alexandra, Goncharova, Maria, Novichkova, Galina, Maschan, Michael, Karachunskiy, Alexander, Olshanskaya, Yulia, Popov, Alexander
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container_title International journal of laboratory hematology
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creator Demina, Irina
Zerkalenkova, Elena
Soldatkina, Olga
Kazakova, Anna
Semchenkova, Alexandra
Goncharova, Maria
Novichkova, Galina
Maschan, Michael
Karachunskiy, Alexander
Olshanskaya, Yulia
Popov, Alexander
description Introduction In this study, we aimed to compare the immunophenotype of tumor cells in children with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the related protein thymic stromal lymphopoietin receptor (TSLPR). Methods We examined bone marrow samples from 46 patients with primary BCP‐ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(−) cohort. TSLPR expression was studied by flow cytometry. Results The majority of CRLF2(+) patients were conventionally positive (≥20% positive cells) for TSLPR (33 of 46, 71.7%). Among the remaining children in this group, two were completely TSLPR‐negative, seven had less than 10% TSLPR‐positive cells, and four had between 10% and 20% TSLPR‐positive cells. By contrast, the majority of CRLF2(−) patients had no TSLPR‐positive cells (119 of 140, 85.0%), while in 15 cases (10.7%), the percentage of TSLPR‐positive cells was below 10%, and in six cases (4.3%), it was between 10% and 20%. Receiver operator characteristic analysis revealed a threshold of only 1.6% TSLPR‐positive cells for the effective prediction of the presence of CRLF2 rearrangement. Moreover, this threshold retained its predictive value when only children with low TSLPR positivity were studied. Conclusion When surface TSLPR is detected at the diagnosis of BCP‐ALL, close attention should be given to the search for chromosomal aberrations involving CRLF2 at any level of expression.
doi_str_mv 10.1111/ijlh.14028
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Methods We examined bone marrow samples from 46 patients with primary BCP‐ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(−) cohort. TSLPR expression was studied by flow cytometry. Results The majority of CRLF2(+) patients were conventionally positive (≥20% positive cells) for TSLPR (33 of 46, 71.7%). Among the remaining children in this group, two were completely TSLPR‐negative, seven had less than 10% TSLPR‐positive cells, and four had between 10% and 20% TSLPR‐positive cells. By contrast, the majority of CRLF2(−) patients had no TSLPR‐positive cells (119 of 140, 85.0%), while in 15 cases (10.7%), the percentage of TSLPR‐positive cells was below 10%, and in six cases (4.3%), it was between 10% and 20%. Receiver operator characteristic analysis revealed a threshold of only 1.6% TSLPR‐positive cells for the effective prediction of the presence of CRLF2 rearrangement. Moreover, this threshold retained its predictive value when only children with low TSLPR positivity were studied. Conclusion When surface TSLPR is detected at the diagnosis of BCP‐ALL, close attention should be given to the search for chromosomal aberrations involving CRLF2 at any level of expression.</description><identifier>ISSN: 1751-5521</identifier><identifier>EISSN: 1751-553X</identifier><identifier>DOI: 10.1111/ijlh.14028</identifier><identifier>PMID: 36748719</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Children ; Chromosome Aberrations ; CRLF2 ; Flow cytometry ; Gene Rearrangement ; Humans ; Leukemia ; Lymphatic leukemia ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Receptors, Cytokine - genetics ; Thymic Stromal Lymphopoietin ; Thymus ; Tumor cells</subject><ispartof>International journal of laboratory hematology, 2023-06, Vol.45 (3), p.337-343</ispartof><rights>2023 John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3578-7557b7d6acdb785456b9bd2b73998a4761b9e03285c158cc9d22d42f71cc33d93</citedby><cites>FETCH-LOGICAL-c3578-7557b7d6acdb785456b9bd2b73998a4761b9e03285c158cc9d22d42f71cc33d93</cites><orcidid>0000-0002-0889-6986 ; 0000-0001-9634-5828 ; 0000-0002-7082-1694</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36748719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Demina, Irina</creatorcontrib><creatorcontrib>Zerkalenkova, Elena</creatorcontrib><creatorcontrib>Soldatkina, Olga</creatorcontrib><creatorcontrib>Kazakova, Anna</creatorcontrib><creatorcontrib>Semchenkova, Alexandra</creatorcontrib><creatorcontrib>Goncharova, Maria</creatorcontrib><creatorcontrib>Novichkova, Galina</creatorcontrib><creatorcontrib>Maschan, Michael</creatorcontrib><creatorcontrib>Karachunskiy, Alexander</creatorcontrib><creatorcontrib>Olshanskaya, Yulia</creatorcontrib><creatorcontrib>Popov, Alexander</creatorcontrib><title>Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B‐lineage acute lymphoblastic leukemia</title><title>International journal of laboratory hematology</title><addtitle>Int J Lab Hematol</addtitle><description>Introduction In this study, we aimed to compare the immunophenotype of tumor cells in children with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the related protein thymic stromal lymphopoietin receptor (TSLPR). Methods We examined bone marrow samples from 46 patients with primary BCP‐ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(−) cohort. TSLPR expression was studied by flow cytometry. Results The majority of CRLF2(+) patients were conventionally positive (≥20% positive cells) for TSLPR (33 of 46, 71.7%). Among the remaining children in this group, two were completely TSLPR‐negative, seven had less than 10% TSLPR‐positive cells, and four had between 10% and 20% TSLPR‐positive cells. By contrast, the majority of CRLF2(−) patients had no TSLPR‐positive cells (119 of 140, 85.0%), while in 15 cases (10.7%), the percentage of TSLPR‐positive cells was below 10%, and in six cases (4.3%), it was between 10% and 20%. Receiver operator characteristic analysis revealed a threshold of only 1.6% TSLPR‐positive cells for the effective prediction of the presence of CRLF2 rearrangement. Moreover, this threshold retained its predictive value when only children with low TSLPR positivity were studied. Conclusion When surface TSLPR is detected at the diagnosis of BCP‐ALL, close attention should be given to the search for chromosomal aberrations involving CRLF2 at any level of expression.</description><subject>Acute lymphoblastic leukemia</subject><subject>Children</subject><subject>Chromosome Aberrations</subject><subject>CRLF2</subject><subject>Flow cytometry</subject><subject>Gene Rearrangement</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Receptors, Cytokine - genetics</subject><subject>Thymic Stromal Lymphopoietin</subject><subject>Thymus</subject><subject>Tumor cells</subject><issn>1751-5521</issn><issn>1751-553X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kcGK1DAYx4Mo7rp68QEk4EWEWZukadqjDq67MiCIgreQpl-nGdOkJinr3HwE38b38UnMbMc5eDCXBPL7_74P_gg9JcUlyeeV2dnhkpQFre-hcyI4WXHOvtw_vSk5Q49i3BUFF2XRPERnrBJlLUhzjn6tfQhgVTLeYd_jNACOc-iVBgzfpwAxnn72o9E4puBHZbHdj9PgJ28gGYcDaJiSD_jWpOFOcoiCy5YcXX_cXFG8BQcZVCEot4URXIo4R_VgbBfALdE3v3_8tMaB2gJWek5wHNRaFVMeb2H-CqNRj9GDXtkIT473Bfp89fbT-nq1-fDuZv16s9KMi3olOBet6Cqlu1bUvORV27QdbQVrmlqVoiJtAwWjNdeE11o3HaVdSXtBtGasa9gFerF4p-C_zRCTHE3UYK1y4OcoqRAlrZqqoBl9_g-683NweTtJa8LKmrLqQL1cKB18jAF6OQUzqrCXpJCHOuWhTnlXZ4afHZVzO0J3Qv_2lwGyALfGwv4_KnnzfnO9SP8ALBevMw</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Demina, Irina</creator><creator>Zerkalenkova, Elena</creator><creator>Soldatkina, Olga</creator><creator>Kazakova, Anna</creator><creator>Semchenkova, Alexandra</creator><creator>Goncharova, Maria</creator><creator>Novichkova, Galina</creator><creator>Maschan, Michael</creator><creator>Karachunskiy, Alexander</creator><creator>Olshanskaya, Yulia</creator><creator>Popov, Alexander</creator><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>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0889-6986</orcidid><orcidid>https://orcid.org/0000-0001-9634-5828</orcidid><orcidid>https://orcid.org/0000-0002-7082-1694</orcidid></search><sort><creationdate>202306</creationdate><title>Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B‐lineage acute lymphoblastic leukemia</title><author>Demina, Irina ; Zerkalenkova, Elena ; Soldatkina, Olga ; Kazakova, Anna ; Semchenkova, Alexandra ; Goncharova, Maria ; Novichkova, Galina ; Maschan, Michael ; Karachunskiy, Alexander ; Olshanskaya, Yulia ; Popov, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3578-7557b7d6acdb785456b9bd2b73998a4761b9e03285c158cc9d22d42f71cc33d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Children</topic><topic>Chromosome Aberrations</topic><topic>CRLF2</topic><topic>Flow cytometry</topic><topic>Gene Rearrangement</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Receptors, Cytokine - genetics</topic><topic>Thymic Stromal Lymphopoietin</topic><topic>Thymus</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Demina, Irina</creatorcontrib><creatorcontrib>Zerkalenkova, Elena</creatorcontrib><creatorcontrib>Soldatkina, Olga</creatorcontrib><creatorcontrib>Kazakova, Anna</creatorcontrib><creatorcontrib>Semchenkova, Alexandra</creatorcontrib><creatorcontrib>Goncharova, Maria</creatorcontrib><creatorcontrib>Novichkova, Galina</creatorcontrib><creatorcontrib>Maschan, Michael</creatorcontrib><creatorcontrib>Karachunskiy, Alexander</creatorcontrib><creatorcontrib>Olshanskaya, Yulia</creatorcontrib><creatorcontrib>Popov, Alexander</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of laboratory hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demina, Irina</au><au>Zerkalenkova, Elena</au><au>Soldatkina, Olga</au><au>Kazakova, Anna</au><au>Semchenkova, Alexandra</au><au>Goncharova, Maria</au><au>Novichkova, Galina</au><au>Maschan, Michael</au><au>Karachunskiy, Alexander</au><au>Olshanskaya, Yulia</au><au>Popov, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B‐lineage acute lymphoblastic leukemia</atitle><jtitle>International journal of laboratory hematology</jtitle><addtitle>Int J Lab Hematol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>45</volume><issue>3</issue><spage>337</spage><epage>343</epage><pages>337-343</pages><issn>1751-5521</issn><eissn>1751-553X</eissn><abstract>Introduction In this study, we aimed to compare the immunophenotype of tumor cells in children with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) harboring rearrangements of the CRLF2 gene with that in children without such aberrations with a specific focus on the surface expression of the related protein thymic stromal lymphopoietin receptor (TSLPR). Methods We examined bone marrow samples from 46 patients with primary BCP‐ALL who had CRLF2 rearrangements detected by FISH (CRLF2(+) cohort). A total of 140 consecutive patients with intact CRLF2 were included in a control CRLF2(−) cohort. TSLPR expression was studied by flow cytometry. Results The majority of CRLF2(+) patients were conventionally positive (≥20% positive cells) for TSLPR (33 of 46, 71.7%). Among the remaining children in this group, two were completely TSLPR‐negative, seven had less than 10% TSLPR‐positive cells, and four had between 10% and 20% TSLPR‐positive cells. By contrast, the majority of CRLF2(−) patients had no TSLPR‐positive cells (119 of 140, 85.0%), while in 15 cases (10.7%), the percentage of TSLPR‐positive cells was below 10%, and in six cases (4.3%), it was between 10% and 20%. Receiver operator characteristic analysis revealed a threshold of only 1.6% TSLPR‐positive cells for the effective prediction of the presence of CRLF2 rearrangement. Moreover, this threshold retained its predictive value when only children with low TSLPR positivity were studied. Conclusion When surface TSLPR is detected at the diagnosis of BCP‐ALL, close attention should be given to the search for chromosomal aberrations involving CRLF2 at any level of expression.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36748719</pmid><doi>10.1111/ijlh.14028</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-0889-6986</orcidid><orcidid>https://orcid.org/0000-0001-9634-5828</orcidid><orcidid>https://orcid.org/0000-0002-7082-1694</orcidid></addata></record>
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subjects Acute lymphoblastic leukemia
Children
Chromosome Aberrations
CRLF2
Flow cytometry
Gene Rearrangement
Humans
Leukemia
Lymphatic leukemia
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Receptors, Cytokine - genetics
Thymic Stromal Lymphopoietin
Thymus
Tumor cells
title Correlation of the surface expression of thymic stromal lymphopoietin receptor with the presence of CRLF2 gene rearrangements in children with B‐lineage acute lymphoblastic leukemia
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