AUTHOR=Lin Danna , Yang Keyan , Yu Lihua , Huang Lulu , Lai Xiaorong , Wu Li , Xia Xiayu , Zhang Jingwen , Zheng Qinlong , Yang Lihua 

TITLE=Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level of CRLF2 gene expression in distinct molecular subtypes

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1256054

DOI=10.3389/fonc.2023.1256054

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Overexpression 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 <italic>CRLF2</italic> overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate <italic>CRLF2</italic> expression level in patients has not been fully elucidated.</p></sec><sec><title>Methods</title><p>In this study, the prognostic impact of <italic>CRLF2</italic> 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 <italic>CRLF2</italic> expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of <italic>CRLF2</italic> in both the Zhujiang Hospital cohort and the TARGET cohort.</p></sec><sec><title>Results</title><p>We used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of <italic>CRLF2</italic> expression. <italic>CRLF2</italic>-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in <italic>CRLF2</italic>-high patients were higher than those in <italic>CRLF2</italic>-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that <italic>CRLF2</italic> overexpression could be subdivided by <italic>CRLF2</italic> expression levels into 2 categories: <italic>CRLF2</italic>-high with a poor survival and <italic>CRLF2</italic>-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to <italic>CLRF2</italic> upregulation, where the <italic>CRLF2</italic> overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL.</p></sec><sec><title>Conclusion</title><p>This study highlights the importance of the molecular mechanisms of the upregulation of <italic>CRLF2</italic> expression in predicting the prognosis of pediatric B-ALL patients.</p></sec>