ArticleCell cycle (Georgetown, Tex.)2014
MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Palbociclib in combination with dexamethasone, bortezomib, and doxorubicin for pediatric relapsed acute lymphoblastic leukemia.Blood neoplasia · 2026Article
- CDK6 inactivation counteracts CALR-mutant-induced MPN evolution and sensitizes MPN stem cells to interferon-α treatment.HemaSphere · 2026Article
- Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma.Nature communications · 2023Article
- Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia.Experimental hematology & oncology · 2023Article
- Palbociclib in Acute Leukemias WithHemaSphere · 2023Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy.Hematology. American Society of Hematology. Education Program · 2022Article
- Elevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms.Cancer discovery · 2022Article
- PROTACs: The Future of Leukemia Therapeutics.Frontiers in cell and developmental biology · 2022Review
- Childhood Acute B-Lineage Lymphoblastic Leukemia With CDKN2A/B Deletion Is a Distinct Entity With Adverse Genetic Features and Poor Clinical Outcomes.Frontiers in oncology · 2022Article
- Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.Cell reports · 2021Article
- Review
- Identification of survival-related alternative splicing signatures in acute myeloid leukemia.Bioscience reports · 2021Article
- Review
- Bortezomib suppresses self-renewal and leukemogenesis of leukemia stem cell by NF-ĸB-dependent inhibition of CDK6 in MLL-rearranged myeloid leukemia.Journal of cellular and molecular medicine · 2021Article
- The RUNX1/RUNX1T1 network: translating insights into therapeutic options.Experimental hematology · 2021Review
- Drug Repurposing for Targeting Acute Leukemia WithFrontiers in pharmacology · 2021Review
- The role of CDK6 in cancer.International journal of cancer · 2020Review
- CRISPR Gene Editing of Murine Blood Stem and Progenitor Cells Induces MLL-AF9 Chromosomal Translocation and MLL-AF9 Leukaemogenesis.International journal of molecular sciences · 2020Article
- CDK6 Inhibition: A Novel Approach in AML Management.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lymphoblastic leukemia in infants (< 1 year-of-age) is characterized by a high incidence of MLL rearrangements. Recently, direct targets of the MLL fusion protein have been identified. However, functional validation of the identified targets remained unacknowledged. In this study, we identify CDK6 as a direct target of the MLL fusion protein and an important player in the proliferation advantage of MLL-rearranged leukemia. CDK6 mRNA was significantly higher expressed in MLL-rearranged infant ALL patients compared with MLL wild-type ALL patients (P < 0.001). Decrease of MLL-AF4 and MLL-ENL fusion mRNA expression by siRNAs resulted in downregulation of CDK6, affirming a direct relationship between the presence of the MLL fusion and CDK6 expression. Knockdown of CDK6 itself significantly inhibited proliferation in the MLL-AF4-positive cell line SEM, whereas knockdown of the highly homologous gene CDK4 had virtually no effect on the cell cycle. Furthermore, we show in vitro sensitivity of MLL-rearranged leukemia cell lines to the CDK4/6-inhibitor PD0332991, inducing a remarkable G 1 arrest, and downregulation of its downstream targets pRB1 and EZH2. We therefore conclude that CDK6 is indeed a direct target of MLL fusion proteins, playing an important role in the proliferation advantage of MLL-rearranged ALL cells.
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