ArticleMolecular oncology2013
p27kip1 maintains a subset of leukemia stem cells in the quiescent state in murine MLL-leukemia.
Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression.Nature communications · 2026Article
- Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia.Stem cell reports · 2024Article
- Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.Cancer metastasis reviews · 2023Review
- Myc-Miz1 signaling promotes self-renewal of leukemia stem cells by repressing Cebpα and Cebpδ.Blood · 2020Article
- High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia.Journal of translational medicine · 2019Article
- The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.Nature communications · 2019Article
- miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.The Journal of experimental medicine · 2018Article
- The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner.Nucleic acids research · 2017Article
- MLL-TET1 fusion protein promotes immortalization of myeloid progenitor cells and leukemia development.Haematologica · 2017Article
- Sensitizing acute myeloid leukemia cells to induced differentiation by inhibiting the RIP1/RIP3 pathway.Leukemia · 2017Article
- CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27Haematologica · 2017Article
- Sensitizing leukemia stem cells to NF-κB inhibitor treatment in vivo by inactivation of both TNF and IL-1 signaling.Oncotarget · 2017Article
- An ShRNA Screen Identifies MEIS1 as a Driver of Malignant Peripheral Nerve Sheath Tumors.EBioMedicine · 2016Article
- Article
- Proteasome inhibitors evoke latent tumor suppression programs in pro-B MLL leukemias through MLL-AF4.Cancer cell · 2014Article
- p27kip1 maintains a subset of leukemia stem cells in the quiescent state in murine MLL-leukemia.Molecular oncology · 2013Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
MLL (mixed-lineage leukemia)-fusion genes induce the development of leukemia through deregulation of normal MLL target genes, such as HOXA9 and MEIS1. Both HOXA9 and MEIS1 are required for MLL-fusion gene-induced leukemogenesis. Co-expression of HOXA9 and MEIS1 induces acute myeloid leukemia (AML) similar to that seen in mice in which MLL-fusion genes are over-expressed. p27(kip1) (p27 hereafter), a negative regulator of the cell cycle, has also been defined as an MLL target, the expression of which is up-regulated in MLL leukemic cells (LCs). To investigate whether p27 plays a role in the pathogenesis of MLL-leukemia, we examined the effects of p27 deletion (p27(-/-)) on MLL-AF9 (MA9)-induced murine AML development. HOXA9/MEIS1 (H/M)-induced, p27 wild-type (p27(+/+)) and p27(-/-) AML were studied in parallel as controls. We found that LCs from both MA9-AML and H/M-AML can be separated into three fractions, a CD117(-)CD11b(hi) differentiated fraction as well as CD117(+)CD11b(hi) and CD117(+)CD11b(lo), two less differentiated fractions. The CD117(+)CD11b(lo) fraction, comprising only 1-3% of total LCs, expresses higher levels of early hematopoietic progenitor markers but lower levels of mature myeloid cell markers compared to other populations of LCs. p27 is expressed and is required for maintaining the quiescent and drug-resistant states of the CD117(+)CD11b(lo) fraction of MA9-LCs but not of H/M-LCs. p27 deletion significantly compromises the leukemogenic capacity of CD117(+)CD11b(lo) MA9-LCs by reducing the frequency of leukemic stem cells (LSCs) but does not do so in H/M-LCs. In addition, we found that p27 is highly expressed and required for cell cycle arrest in the CD117(-)CD11b(hi) fraction in both types of LCs. Furthermore, we found that c-Myc expression is required for maintaining LCs in an undifferentiated state independently of proliferation. We concluded that p27 represses the proliferation of LCs, which is specifically required for maintaining the quiescent and drug-resistant states of a small subset of MA9-LSCs in collaboration with the differentiation blockage function of c-Myc.
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