Evidence map›Paper›PMID 34937317›Full record

ArticleHaematologica2022

Rational drug combinations with CDK4/6 inhibitors in acute lymphoblastic leukemia.

Karen L Bride, Hai Hu, Anastasia Tikhonova, Tori J Fuller, Tiffaney L Vincent, Rawan Shraim, Marilyn M Li, William L Carroll, Elizabeth A Raetz, Iannis Aifantis and 1 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
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  14. [Research progress on copy number alterations in pediatric B-cell acute lymphoblastic leukemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Palbociclib as an Antitumor Drug: A License to Kill.Molecules (Basel, Switzerland) · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Karen L BrideDepartment of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park.
Hai HuPerlmutter Cancer Center and Department of Pediatrics, NYU Langone Health, NY, NY.
Anastasia TikhonovaPrincess Margaret Cancer Centre, University of Toronto, Toronto, ON.
Tori J FullerChildren's Hospital of Philadelphia; Philadelphia, PA.
Tiffaney L VincentChildren's Hospital of Philadelphia; Philadelphia, PA.
Rawan ShraimChildren's Hospital of Philadelphia; Philadelphia, PA.
Marilyn M LiChildren's Hospital of Philadelphia; Philadelphia, PA.
William L CarrollPerlmutter Cancer Center and Department of Pediatrics, NYU Langone Health, NY, NY.
Elizabeth A RaetzPerlmutter Cancer Center and Department of Pediatrics, NYU Langone Health, NY, NY.
Iannis AifantisPerlmutter Cancer Center and Department of Pediatrics, NYU Langone Health, NY, NY.
David T TeacheyChildren's Hospital of Philadelphia; Philadelphia, PA.
Children's Hospital of Philadelphia · USNYU Langone Health · USCohen Children's Medical Center · USPhiladelphia University · USUniversity of Toronto · CA

Funding

Improving risk allocation and developing novel therapies for children with T-ALL and T-LLR01CA193776 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Terzah M Horton, ADAM B OLSHEN · 2015 to 2026
$6.2M
COG NCTN Integrated Translational Science Center for Hematopoietic Malignancies in ChildrenUG1CA233249 · NCI · PUBLIC HEALTH INSTITUTE · PI MESHINCHI, SOHEIL · 2019 to 2025
$4.9M
Biomarkers of dasatinib response and resistance in T-cell acute lymphoblastic leukemiaR01CA264837 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI TEACHEY, DAVID T., YANG, JUN J. · 2021 to 2025
$3.0M
Genomic Profiling of T-cell Acute Lymphoblastic Leukemia in ChildrenR03CA256550 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI MULLIGHAN, CHARLES G., TEACHEY, DAVID T. · 2021 to 2021
$382k
NCI NIH HHS R01 CA193776NCI NIH HHS R01 CA264837NCI NIH HHS R03 CA256550NCI NIH HHS UG1 CA233249
6 · The paper itself

Abstract

Despite improvements in outcomes for children with B- and T-cell acute lymphoblastic leukemia (B-ALL and T-ALL), patients with resistant or relapsed disease fare poorly. Previous studies have demonstrated the essential role of cyclin D3 in T-ALL disease initiation and progression and that targeting of the CDK4/6-cyclin D complex can suppress T-ALL proliferation, leading to efficient cell death in animal models. Studies in leukemia and other malignancies, suggest that schedule is important when combining CDK4/6 inhibitors (CDKi) with cytotoxic agents. Based on these observations, we broadened evaluation of two CDKi, palbociclib (PD-0332991, Pfizer) and ribociclib (LEE011, Novartis) in B- and T-ALL as single agent and in combination with conventional cytotoxic chemotherapy, using different schedules in preclinical models. As monotherapy, CDKi caused cell cycle arrest with a significant decrease in S phase entry and were active in vivo across a broad number of patient-derived xenograft samples. Prolonged monotherapy induces resistance, for which we identified a potential novel mechanism using transcriptome profiling. Importantly, simultaneous but not sequential treatment of CDKi with conventional chemotherapy (dexamethasone, L-asparaginase and vincristine) led to improved efficacy compared to monotherapy in vivo. We provide novel evidence that combining CDKi and conventional chemotherapy can be safe and effective. These results led to the rational design of a clinical trial.

Indexed as

Precursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaAnimalsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Drug CombinationsHumansProtein Kinase InhibitorsCDK4 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Drug CombinationsProtein Kinase Inhibitors

Identifiers

PMID34937317
PMCPMC9335101
OpenAlexW4200289889

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.