IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia
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Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
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Fimlab Laboratories, Department of Pathology, Tampere University Hospital, 33520 Tampere, Finland
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Department of Biological and Environmental Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland
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Institute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland
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Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland
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Department of Pathology, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
7
Tays Cancer Centre, Tampere University Hospital, 33520 Tampere, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Ajay Pratap Singh
Cancers 2021, 13(7), 1505; https://doi.org/10.3390/cancers13071505
Received: 13 February 2021
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Revised: 11 March 2021
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Accepted: 22 March 2021
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Published: 25 March 2021
(This article belongs to the Collection The Biomarkers for the Diagnosis and Prognosis in Cancer)
Simple Summary
Although the prognosis of acute lymphoblastic leukemia (ALL) has improved significantly during the past decades, ALL remains a major cause of pediatric cancer mortality, and more accurate risk-stratification is required. We investigated IGF2BP3, which has previously been associated with aggressive cancers, and found high and subtype-specific expression of IGF2BP3 in B-cell ALL, that was associated with good outcome in high-risk patients. Results suggest that IGF2BP3 could be useful to improve stratification and prognosis of B-ALL.
The oncofetal protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) belongs to a family of RNA-binding proteins involved in localization, stability, and translational regulation of target RNAs. IGF2BP3 is used as a diagnostic and prognostic marker in several malignancies. Although the prognosis of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved, a subgroup of patients exhibits high-risk features and suffer from disease recurrence. We sought to identify additional biomarkers to improve diagnostics, and we assessed expression of IGF2BP3 in a population-based pediatric cohort of B-ALL using a tissue microarray platform. The majority of pediatric B-ALL cases were positive for IGF2BP3 immunohistochemistry and were associated with an increased proliferative phenotype and activated STAT5 signaling pathway. Two large gene expression data sets were probed for the expression of IGF2BP3—the highest levels were seen among the B-cell lymphomas of a germinal center origin and well-established (KMT2A-rearranged and ETV6-RUNX1) and novel subtypes of B-ALL (e.g., NUTM1 and ETV6-RUNX1-like). A high mRNA for IGF2BP3 was associated with a proliferative “metagene” signature and a high expression of CDK6 in B-ALL. A low expression portended inferior survival in a high-risk cohort of pediatric B-ALL. Overall, our results show that IGF2BP3 shows subtype-specificity in expression and provides prognostic utility in high-risk B-ALL.
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Keywords:
insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3); mRNA; pediatric B-cell acute lymphoblastic leukemia; prognosis; proliferation; protein
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MDPI and ACS Style
Mäkinen, A.; Nikkilä, A.; Haapaniemi, T.; Oksa, L.; Mehtonen, J.; Vänskä, M.; Heinäniemi, M.; Paavonen, T.; Lohi, O. IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia. Cancers 2021, 13, 1505. https://doi.org/10.3390/cancers13071505
AMA Style
Mäkinen A, Nikkilä A, Haapaniemi T, Oksa L, Mehtonen J, Vänskä M, Heinäniemi M, Paavonen T, Lohi O. IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia. Cancers. 2021; 13(7):1505. https://doi.org/10.3390/cancers13071505
Chicago/Turabian StyleMäkinen, Artturi, Atte Nikkilä, Teppo Haapaniemi, Laura Oksa, Juha Mehtonen, Matti Vänskä, Merja Heinäniemi, Timo Paavonen, and Olli Lohi. 2021. "IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia" Cancers 13, no. 7: 1505. https://doi.org/10.3390/cancers13071505
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