ArticleBlood2014
Requirement for CDK6 in MLL-rearranged acute myeloid leukemia.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 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.
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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
117 citing papers in PubMed, 175 citations in OpenAlex.
- Palbociclib in combination with dexamethasone, bortezomib, and doxorubicin for pediatric relapsed acute lymphoblastic leukemia.Blood neoplasia · 2026Article
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- A Type II CDK6 Degrader Enables Cellular Targeting beyond the Limits of Type II Inhibition.Journal of the American Chemical Society · 2026Article
- CDK6 inactivation counteracts CALR-mutant-induced MPN evolution and sensitizes MPN stem cells to interferon-α treatment.HemaSphere · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Combined Menin and XPO1 inhibition drive synergistic antileukemic activity inbioRxiv : the preprint server for biology · 2026Article
- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- Synergistic potential of CDK4/6 inhibitors and ATRA in non-APL AML.British journal of haematology · 2025Article
- Image-based drug screening combined with molecular profiling identifies signatures and drivers of therapy resistance in pediatric AML.Cell reports. Medicine · 2025Article
- Targeting chromatin modifying complexes in acute myeloid leukemia.Stem cells translational medicine · 2025Review
- CDK6-Dependent, CDK4-Independent Synovial Hyperplasia in Arthritic Mice and Tumor Necrosis Factor-α-Induced Proliferation of Synovial Fibroblasts.International journal of molecular sciences · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia.Cancers · 2025Article
- NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities.HemaSphere · 2024Review
- Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition inInternational journal of molecular sciences · 2024Article
- Narazaciclib, a novel multi-kinase inhibitor with potent activity against CSF1R, FLT3 and CDK6, shows strong anti-AML activity in defined preclinical models.Scientific reports · 2024Article
- PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies.British journal of cancer · 2023Article
- Article
- Palbociclib in Acute Leukemias WithHemaSphere · 2023Article
- Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 14 institutions in 3 countries.
Funding
Abstract
Chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) trigger aberrant gene expression in hematopoietic progenitors and give rise to an aggressive subtype of acute myeloid leukemia (AML). Insights into MLL fusion-mediated leukemogenesis have not yet translated into better therapies because MLL is difficult to target directly, and the identity of the genes downstream of MLL whose altered transcription mediates leukemic transformation are poorly annotated. We used a functional genetic approach to uncover that AML cells driven by MLL-AF9 are exceptionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the preferential growth inhibition induced by CDK6 depletion is mediated through enhanced myeloid differentiation. CDK6 essentiality is also evident in AML cells harboring alternate MLL fusions and a mouse model of MLL-AF9-driven leukemia and can be ascribed to transcriptional activation of CDK6 by mutant MLL. Importantly, the context-dependent effects of lowering CDK6 expression are closely phenocopied by a small-molecule CDK6 inhibitor currently in clinical development. These data identify CDK6 as critical effector of MLL fusions in leukemogenesis that might be targeted to overcome the differentiation block associated with MLL-rearranged AML, and underscore that cell-cycle regulators may have distinct, noncanonical, and nonredundant functions in different contexts.
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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.