Evidence map›Paper›PMID 36700399›Full record

ArticleHaematologica2023

Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia.

Holly Pariury, Joshua Fandel, Stefanie Bachl, Kenny K Ang, Sarine Markossian, Chris G Wilson, Benjamin S Braun, Bogdan Popescu, Margo Wohlfeil, Kyle Beckman and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

17 authors at 3 institutions in 1 country.

Holly PariuryDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco; CA; Department of Pediatrics, Banner University Medical Center and the University of Arizona Cancer Center, Tucson; AZ.
Joshua FandelDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Stefanie BachlDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Kenny K AngSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California.
Sarine MarkossianSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California.
Chris G WilsonSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California.
Benjamin S BraunDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Bogdan PopescuDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco.
Margo WohlfeilDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Kyle BeckmanDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Simayijiang XirenayiDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California.
Ritu P RoyDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco.
Adam B OlshenComputation Biology and Informatics Core at the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco; CA; Department of Epidemiology and Biostatistics, University of California.
Catherine SmithDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco.
Michelle R ArkinSmall Molecule Discovery Center, Department of Pharmaceutical Chemistry, University of California.
Mignon L LohBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
Ernesto Diaz-FloresDepartment of Pediatrics, Benioff Children's Hospital, and the Helen Diller Family Comprehensive Cancer Center, University of California. ernesto.diaz-flores@ucsf.edu.
UCSF Benioff Children's Hospital · USUniversity of California, San Francisco · USSeattle Children's Hospital · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
NCI NIH HHS P30 CA082103
6 · The paper itself

Abstract

Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive blood cancer with a poor prognosis despite intensive chemotherapy or stem cell transplant. Children and adolescents with positive end-of-induction minimal residual disease have an overall survival lower than 30%. However, data regarding therapeutic alternatives for this disease is nearly nonexistent, emphasizing the critical need for new or adjunctive therapies that can improve outcomes. We previously reported on the therapeutic efficacy of venetoclax (ABT-199) in hypodiploid B-lineage ALL but with limitations as monotherapy. In this study, we set out to identify drugs enhancing the anti-leukemic effect of venetoclax in hypodiploid ALL. Using a highthroughput drug screen, we identified dinaciclib, a cyclin-dependent kinase inhibitor that worked synergistically with venetoclax to induce cell death in hypodiploid cell lines. This combination eradicated leukemic blasts within hypodiploid ALL patient-derived xenografts mice with low off-target toxicity. Our findings suggest that dual inhibition of BCL-2 (venetoclax) and CDK9/MCL-1 (dinaciclib) is a promising therapeutic approach in hypodiploid ALL, warranting further investigation to inform clinical trials in this high-risk patient population.

Indexed as

Antineoplastic AgentsPrecursor Cell Lymphoblastic Leukemia-LymphomaAnimalsApoptosisBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCyclic N-OxidesHumansIndolizinesMiceMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Pyridinium CompoundsSulfonamidesAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCyclic N-OxidesdinaciclibIndolizinesMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Pyridinium CompoundsSulfonamidesvenetoclax

Identifiers

PMID36700399
PMCPMC10153511
OpenAlexW4318065390

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.