Trial reportBlood2020
Impaired condensin complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL.
Trial report in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.Clinical and experimental medicine · 2025Review
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
- The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia.Leukemia · 2024Article
- Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.EMBO molecular medicine · 2024Article
- Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia.Nature communications · 2023Article
- Centrosome Amplification Is a Potential Molecular Target in Paediatric Acute Lymphoblastic Leukemia.Cancers · 2022Article
- Hyperdiploidy: the longest known, most prevalent, and most enigmatic form of acute lymphoblastic leukemia in children.Leukemia · 2022Review
- Condensin I and condensin II proteins form a LINE-1 dependent super condensin complex and cooperate to repress LINE-1.Nucleic acids research · 2022Article
- Article
- Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia.Molecular oncology · 2022Article
- An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse.BMC genomic data · 2022Article
- The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia.Cancers · 2022Article
- Engraftment characterization of risk-stratified AML in NSGS mice.Blood advances · 2021Article
- Infectious triggers and novel therapeutic opportunities in childhood B cell leukaemia.Nature reviews. Immunology · 2021Review
- Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2021Review
- Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia.Genes, chromosomes & cancer · 2021Article
- Somatic Sex: On the Origin of Neoplasms With Chromosome Counts in Uneven Ploidy Ranges.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 11 institutions in 4 countries.
Funding
Abstract
B-cell acute lymphoblastic leukemia (ALL; B-ALL) is the most common pediatric cancer, and high hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD being an initiating oncogenic event affiliated with childhood B-ALL, the mitotic and chromosomal defects associated with HyperD B-ALL (HyperD-ALL) remain poorly characterized. Here, we have used 54 primary pediatric B-ALL samples to characterize the cellular-molecular mechanisms underlying the mitotic/chromosome defects predicated to be early pathogenic contributors in HyperD-ALL. We report that HyperD-ALL blasts are low proliferative and show a delay in early mitosis at prometaphase, associated with chromosome-alignment defects at the metaphase plate leading to robust chromosome-segregation defects and nonmodal karyotypes. Mechanistically, biochemical, functional, and mass-spectrometry assays revealed that condensin complex is impaired in HyperD-ALL cells, leading to chromosome hypocondensation, loss of centromere stiffness, and mislocalization of the chromosome passenger complex proteins Aurora B kinase (AURKB) and Survivin in early mitosis. HyperD-ALL cells show chromatid cohesion defects and an impaired spindle assembly checkpoint (SAC), thus undergoing mitotic slippage due to defective AURKB and impaired SAC activity, downstream of condensin complex defects. Chromosome structure/condensation defects and hyperdiploidy were reproduced in healthy CD34+ stem/progenitor cells upon inhibition of AURKB and/or SAC. Collectively, hyperdiploid B-ALL is associated with a defective condensin complex, AURKB, and SAC.
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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.