ArticleBlood2011
Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 69 citations in OpenAlex.
- SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Activation of cerebral Ras-related C3 botulinum toxin substrate (Rac) 1 promotes post-ischemic stroke functional recovery in aged mice.Neural regeneration research · 2024Article
- Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9Haematologica · 2024Article
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
- Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment.Genome medicine · 2022Article
- Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects.Blood cancer journal · 2022Article
- Role of Rho GTPases in stem cell regulation.Biochemical Society transactions · 2021Review
- Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas.Biomedicines · 2021Article
- Review
- Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells.Heliyon · 2020Article
- The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling.Blood cancer journal · 2020Article
- RAC2 acts as a prognostic biomarker and promotes the progression of clear cell renal cell carcinoma.International journal of oncology · 2019Article
- Rac GTPases in Hematological Malignancies.International journal of molecular sciences · 2018Review
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
- Turning Stem Cells Bad: Generation of Clinically Relevant Models of Human Acute Myeloid Leukemia through Gene Delivery- or Genome Editing-Based Approaches.Molecules (Basel, Switzerland) · 2018Review
- RHO GTPases in cancer: known facts, open questions, and therapeutic challenges.Biochemical Society transactions · 2018Review
- Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma.Oncotarget · 2018Article
- De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia.Nature communications · 2018Article
- Bruton's tyrosine kinase and RAC1 promote cell survival in MLL-rearranged acute myeloid leukemia.Leukemia · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.
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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.