Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes
BackgroundOverexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1256054/full |
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| author | Danna Lin Keyan Yang Lihua Yu Lulu Huang Xiaorong Lai Li Wu Xiayu Xia Jingwen Zhang Qinlong Zheng Lihua Yang |
| author_facet | Danna Lin Keyan Yang Lihua Yu Lulu Huang Xiaorong Lai Li Wu Xiayu Xia Jingwen Zhang Qinlong Zheng Lihua Yang |
| author_sort | Danna Lin |
| collection | DOAJ |
| description | BackgroundOverexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate CRLF2 expression level in patients has not been fully elucidated.MethodsIn this study, the prognostic impact of CRLF2 expression level on molecular types of B-ALL in pediatric patients from Zhujiang Hospital (n = 111) was retrospectively analyzed. Youden index analysis was used to categorize CRLF2 expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of CRLF2 in both the Zhujiang Hospital cohort and the TARGET cohort.ResultsWe used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of CRLF2 expression. CRLF2-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in CRLF2-high patients were higher than those in CRLF2-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that CRLF2 overexpression could be subdivided by CRLF2 expression levels into 2 categories: CRLF2-high with a poor survival and CRLF2-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to CLRF2 upregulation, where the CRLF2 overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL.ConclusionThis study highlights the importance of the molecular mechanisms of the upregulation of CRLF2 expression in predicting the prognosis of pediatric B-ALL patients. |
| first_indexed | 2024-03-11T12:17:13Z |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-11T12:17:13Z |
| publishDate | 2023-11-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-edf7cb85d64a446a9d10046e45dcfcb72023-11-07T08:17:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-11-011310.3389/fonc.2023.12560541256054Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypesDanna Lin0Keyan Yang1Lihua Yu2Lulu Huang3Xiaorong Lai4Li Wu5Xiayu Xia6Jingwen Zhang7Qinlong Zheng8Lihua Yang9Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaLaboratory of Molecular Diagnostics, Beijing GoBroad Boren Hospital, Beijing, ChinaDepartment of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaLaboratory of Molecular Diagnostics, Beijing GoBroad Boren Hospital, Beijing, ChinaDepartment of Clinical Hematology&Flow Cytometry, Guangzhou KingMed Center for Clinical Lab. Co., Ltd., Guangzhou, ChinaLaboratory of Molecular Diagnostics, Beijing GoBroad Boren Hospital, Beijing, ChinaDepartment of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaBackgroundOverexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate CRLF2 expression level in patients has not been fully elucidated.MethodsIn this study, the prognostic impact of CRLF2 expression level on molecular types of B-ALL in pediatric patients from Zhujiang Hospital (n = 111) was retrospectively analyzed. Youden index analysis was used to categorize CRLF2 expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of CRLF2 in both the Zhujiang Hospital cohort and the TARGET cohort.ResultsWe used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of CRLF2 expression. CRLF2-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in CRLF2-high patients were higher than those in CRLF2-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that CRLF2 overexpression could be subdivided by CRLF2 expression levels into 2 categories: CRLF2-high with a poor survival and CRLF2-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to CLRF2 upregulation, where the CRLF2 overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL.ConclusionThis study highlights the importance of the molecular mechanisms of the upregulation of CRLF2 expression in predicting the prognosis of pediatric B-ALL patients.https://www.frontiersin.org/articles/10.3389/fonc.2023.1256054/fullB-ALLCRLF2Ph-likepediatricleukemia |
| spellingShingle | Danna Lin Keyan Yang Lihua Yu Lulu Huang Xiaorong Lai Li Wu Xiayu Xia Jingwen Zhang Qinlong Zheng Lihua Yang Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes Frontiers in Oncology B-ALL CRLF2 Ph-like pediatric leukemia |
| title | Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes |
| title_full | Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes |
| title_fullStr | Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes |
| title_full_unstemmed | Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes |
| title_short | Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes |
| title_sort | poor outcome of pediatric b cell acute lymphoblastic leukemia associated with high level of crlf2 gene expression in distinct molecular subtypes |
| topic | B-ALL CRLF2 Ph-like pediatric leukemia |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1256054/full |
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