ArticleLeukemia2005
Direct evidence for cooperating genetic events in the leukemic transformation of normal human hematopoietic cells.
Article in Leukemia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 108 citations in OpenAlex.
- Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors.The Journal of clinical investigation · 2013Trial
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- Mitochondrial RNA degradation regulates differentiation, stemness, and immune sensitivity in acute myeloid leukemia.Nature communications · 2026Article
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- MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.Oncotarget · 2022Article
- The metabolic enzyme hexokinase 2 localizes to the nucleus in AML and normal haematopoietic stem and progenitor cells to maintain stemness.Nature cell biology · 2022Article
- IPO11 regulates the nuclear import of BZW1/2 and is necessary for AML cells and stem cells.Leukemia · 2022Article
- Small-molecule inhibitors targeting Polycomb repressive complex 1 RING domain.Nature chemical biology · 2021Article
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- The role of mitochondrial proteases in leukemic cells and leukemic stem cells.Stem cells translational medicine · 2020Article
- SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism.Cell death & disease · 2020Article
- Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness.Nature communications · 2019Article
- Article
- The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.Cell stem cell · 2019Article
- Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.Leukemia · 2019Article
- Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma: preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates.The pharmacogenomics journal · 2018Article
- Article
- SMYD2 lysine methyltransferase regulates leukemia cell growth and regeneration after genotoxic stress.Oncotarget · 2017Article
- Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although genetic abnormalities associated with hematological malignancies are readily identified, the natural history of human leukemia cannot be observed because initiating and subsequent transforming events occur before clinical presentation. Furthermore, it has not been possible to study leukemogenesis in vitro as normal human cells do not spontaneously transform. Thus, the nature and sequence of genetic changes required to convert human hematopoietic cells into leukemia cells have never been directly examined. We have developed a system where the first step in the leukemogenic process is an engineered disruption of differentiation and self-renewal due to expression of the TLS-ERG oncogene, followed in some cases by overexpression of hTERT. In two of 13 experiments, transduced cells underwent step-wise transformation and immortalization through spontaneous acquisition of additional changes. The acquired karyotypic abnormalities and alterations including upregulation of Bmi-1 and telomerase all occur in acute myeloid leukemia (AML), establishing the relevance of this system. One resultant cell line studied in depth exhibits cellular properties characteristic of AML, notably a hierarchical organization initiated by leukemic stem cells that differentiate abnormally. These findings provide direct evidence for multiple cooperating events in human leukemogenesis, and provide a foundation for studying the genetic changes that occur during leukemic initiation and progression.
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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.