ArticlePediatric blood & cancer2014
Ikaros deletions in BCR-ABL-negative childhood acute lymphoblastic leukemia are associated with a distinct gene expression signature but do not result in intrinsic chemoresistance.
Article in Pediatric blood & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Pooled it
- Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia.Cell reports · 2023Article
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- Article
- Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.Blood advances · 2021Article
- Article
- Prognostic Impact of Somatic Copy Number Alterations in Childhood B-Lineage Acute Lymphoblastic Leukemia.Current oncology reports · 2020Review
- Janus Kinase Mutations in Mice Lacking PU.1 and Spi-B Drive B Cell Leukemia through Reactive Oxygen Species-Induced DNA Damage.Molecular and cellular biology · 2020Article
- Mapping and targeting of the leukemic microenvironment.The Journal of experimental medicine · 2020Review
- Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation.PLoS biology · 2019Article
- The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia.Haematologica · 2018Review
- Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome.The Journal of experimental medicine · 2017Article
- Tumor suppressor IKZF1 mediates glucocorticoid resistance in B-cell precursor acute lymphoblastic leukemia.Leukemia · 2016Article
- Effect of IKZF1 deletions on signal transduction pathways in Philadelphia chromosome negative pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL).Experimental hematology & oncology · 2015Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIkaros, the product of IKZF1, is a regulator of lymphoid development and polymorphisms in the gene have been associated with the acute lymphoblastic leukemia (ALL). Additionally, IKZF1 deletions and mutations identify high-risk biological subsets of childhood ALL [Georgopoulos et al. Cell 1995;83(2):289-299; Mullighan et al. N Engl J Md 2009;360(5):470-480]. PROCEDURES: To discover the underlying pathways modulated by Ikaros we performed gene expression and gene ontology analysis in IKZF1 deleted primary B-ALL pediatric patient samples. To validate downstream targets we performed qPCR on individual patient samples. We also created IKZF1 knockdown B-ALL cell lines with over 50% reduction of Ikaros, mimicking haplosufficient Ikaros deletions, and again performed qPCR to investigate the downstream targets. Finally, to understand the association of Ikaros deletion with a poor prognosis we challenged our IKZF1 knockdown cell lines with chemotherapy and compared responses to IKZF1 wild-type controls.
resultsWe report a specific gene expression signature of 735 up-regulated and 473 down-regulated genes in IKZF1 deleted primary B-ALL pediatric patient samples. Gene ontology studies revealed an up-regulation of genes associated with cell adhesion, cytoskeletal regulation, and motility in IKZF deleted patient samples. Validated up-regulated target genes in IKZF1 deleted patient samples included CTNND1 and PVRL2 (P = 0.0003 and P = 0.001), and RAB3IP and SPIB (P = 0.005 and P = 0.032) were down-regulated. In further studies in IKZF1 knockdown cell lines, apoptosis assays showed no significant chemoresistance.
conclusionIKZF1 knockdown alone does not impart intrinsic chemotherapy resistance suggesting that the association with a poor prognosis may be due to additional lesions, microenvironmental interactions with the bone marrow niche, or other factors.
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