ArticleHaematologica2019
Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation.
Article in Haematologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
10 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Regulation of developmentally controlled enhancer activity by extrinsic signals in normal and malignant cells: AP-1 at the centre.Frontiers in epigenetics and epigenomics · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- Review
- RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks.Haematologica · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Review
- HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate.Cancer gene therapy · 2020Article
- Standing at odds: mutated RAS and hematopoietic stem cells.Haematologica · 2019Article
Corrections and comments
- Commented on by
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Somatic mutations in acute myeloid leukemia are acquired sequentially and hierarchically. First, pre-leukemic mutations, such as t(8;21) that encodes AML1-ETO, are acquired within the hematopoietic stem cell (HSC) compartment, while signaling pathway mutations, including KRAS activating mutations, are late events acquired during transformation of leukemic progenitor cells and are rarely detectable in HSC. This raises the possibility that signaling pathway mutations are detrimental to clonal expansion of pre-leukemic HSC. To address this hypothesis, we used conditional genetics to introduce Aml1-ETO and K-RasG12D into murine HSC, either individually or in combination. In the absence of activated Ras, Aml1-ETO-expressing HSC conferred a competitive advantage. However, activated K-Ras had a marked detrimental effect on Aml1-ETO-expressing HSC, leading to loss of both phenotypic and functional HSC. Cell cycle analysis revealed a loss of quiescence in HSC co-expressing Aml1-ETO and K-RasG12D, accompanied by an enrichment in E2F and Myc target gene expression and depletion of HSC self-renewal-associated gene expression. These findings provide a mechanistic basis for the observed absence of KRAS signaling mutations in the pre-malignant HSC compartment.
Indexed as
Identifiers
What OpenQuestion holds
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.