ArticleLeukemia2015
Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK.Leukemia · 2021Article
- Ikaros Proteins in Tumor: Current Perspectives and New Developments.Frontiers in molecular biosciences · 2021Review
- Behind the scenes with basophils: an emerging therapeutic target.Immunotherapy advances · 2021Review
- Regulation of Small GTPase Rab20 by Ikaros in B-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Article
- Ikaros family zinc-finger 1 mutation is an independent factor for the poor prognosis of adult B-cell acute lymphoblastic leukemia, and allogeneic hematopoietic stem cell transplantation can improve clinical outcomes.Bone marrow transplantation · 2019Article
- Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocytes.Cell death & disease · 2018Article
- Review
- Modeling the process of human tumorigenesis.Nature communications · 2017Review
- Article
- The Philadelphia chromosome in leukemogenesis.Chinese journal of cancer · 2016Review
- Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia.The Journal of biological chemistry · 2016Article
- Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.Nature communications · 2015Article
- The transcription factors Ik-1 and MZF1 downregulate IGF-IR expression in NPM-ALK⁺ T-cell lymphoma.Molecular cancer · 2015Article
- Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression.Blood · 2015Article
- Ikaros6 is associated with BCR-ABL1 and myeloid-associated antigens but indicates poor prognosis independently in Chinese adult B-cell acute lymphoblastic leukemia.International journal of clinical and experimental medicine · 2015Article
- Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.Blood cancer journal · 2014Article
- A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells.Stem cell reports · 2014Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Historically, our understanding of mechanisms underlying human leukemogenesis are inferred from genetically engineered mouse models. Relatively, few models that use primary human cells recapitulate the full leukemic transformation as assayed in xenografts and myeloid transformation is infrequent. We report a humanized experimental leukemia model where xenografts develop aggressive acute myeloid leukemia (AML) with disseminated myeloid sarcomas within 4 weeks following transplantation of cord blood transduced with vectors expressing BCR-ABL1 and a dominant-negative isoform of IKAROS, Ik6. Ik6 induced transcriptional programs in BCR-ABL1-transduced progenitors that contained repressed B-cell progenitor programs, along with strong stemness, proliferation and granulocyte-monocytic progenitor (GMP) signatures-a novel combination not induced in control groups. Thus, wild-type IKAROS restrains stemness properties and has tumor suppressor activity in BCR-ABL1-initiated leukemia. Although IKAROS mutations/deletions are common in lymphoid transformation, they are found also at low frequency in AML that progress from a prior myeloproliferative neoplasm (MPN) state. Our experimental system provides an excellent model to gain insight into these rare cases of AML transformation and the properties conferred by IKAROS loss of function as a secondary mutation. More generally, our data points to the importance of deregulated stemness/lineage commitment programs in human myeloid leukemogenesis.
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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.