ArticleOncotarget2016
High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Combination of p-STAT5, CRLF2 and copy number alterations as a potential indicator of a high-risk subgroup of acute lymphoblastic leukemia.Discover oncology · 2026Article
- Article
- A panel of plasma proteins associated with venous thromboembolism in patients with prostate cancer.Cancer biomarkers : section A of Disease markers · 2025Article
- Critical roles of IKAROS and HDAC1 in regulation of heterochromatin and tumor suppression in T-cell acute lymphoblastic leukemia.Leukemia · 2025Article
- Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant-review article.Annals of hematology · 2023Review
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- Poor outcome of pediatric B-cell acute lymphoblastic leukemia associated with high level ofFrontiers in oncology · 2023Article
- Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children.International journal of molecular sciences · 2022Review
- IKZF1 deletions associate with CRLF2 overexpression leading to a poor prognosis in B-cell precursor acute lymphoblastic leukaemia.Translational oncology · 2022Article
- Lymphoid blast transformation in an MPN with BCR-JAK2 treated with ruxolitinib: putative mechanisms of resistance.Blood advances · 2021Article
- Mutational profiling in acute lymphoblastic leukemia by RNA sequencing and chromosomal genomic array testing.Cancer medicine · 2021Article
- Hematological characteristics, cytogenetic features, and post-induction measurable residual disease in thymic stromal lymphopoietin receptor (TSLPR) overexpressed B-cell acute lymphoblastic leukemia in an Indian cohort.Annals of hematology · 2021Observational
- CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.The journal of pathology. Clinical research · 2021Article
- Ikaros Proteins in Tumor: Current Perspectives and New Developments.Frontiers in molecular biosciences · 2021Review
- The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Article
- Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- Cellular signaling and epigenetic regulation of gene expression in leukemia.Advances in biological regulation · 2020Review
- How I diagnose and manage Philadelphia chromosome-like acute lymphoblastic leukemia.Haematologica · 2019Review
- Ikaros tumor suppressor function includes induction of active enhancers and super-enhancers along with pioneering activity.Leukemia · 2019Article
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
Overexpression of cytokine receptor-like factor 2 (CRLF2) due to chromosomal rearrangement has been observed in acute lymphoblastic leukemia (ALL) and reported to contribute to oncogenesis and unfavorable outcome in ALL. We studied B-ALL and T-ALL patients without CRLF2 rearrangement and observed that CRLF2 is significantly increased in a subset of these patients. Our study shows that high CRLF2expression correlates with high-risk ALL markers, as well as poor survival. We found that the IKZF1-encoded protein, Ikaros, directly binds to the CRLF2 promoter and regulates CRLF2 expression in leukemia cells. CK2 inhibitor, which can increase Ikaros activity, significantly increases Ikaros binding in ALL cells and suppresses CRLF2 expression in an Ikaros-dependent manner. CRLF2 expression is significantly higher in patients with IKZF1 deletion as compared to patients without IKZF1 deletion. Treatment with CK2 inhibitor also results in an increase in IKZF1 binding to the CRLF2 promoter and suppression of CRLF2 expression in primary ALL cells. We further observed that CK2 inhibitor induces increased H3K9me3 histone modifications in the CRLF2 promoter in ALL cell lines and primary cells. Taken together, our results demonstrate that high expression of CRLF2 correlates with high-risk ALL and short survival in patients without CRLF2 rearrangement. Our results are the first to demonstrate that the IKZF1-encoded Ikaros protein directly suppresses CRLF2 expression through enrichment of H3K9me3 in its promoter region. Our data also suggest that high CRLF2 expression works with the IKZF1 deletion to drive oncogenesis of ALL and has significance in an integrated prognostic model for adult high-risk ALL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.