Evidence map›Paper›PMID 39071567›Full record

ArticleHeliyon2024

Synergistic drug interactions of the histone deacetylase inhibitor givinostat (ITF2357) in CRLF2-rearranged pediatric B-cell precursor acute lymphoblastic leukemia identified by high-throughput drug screening.

Athanasios Oikonomou, Titus Watrin, Luigia Valsecchi, Katerina Scharov, Angela Maria Savino, Julian Schliehe-Diecks, Michela Bardini, Grazia Fazio, Silvia Bresolin, Andrea Biondi and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

14 authors.

Athanasios OikonomouTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Titus WatrinDepartment of Paediatric Oncology, Haematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Düsseldorf, Germany.
Luigia ValsecchiTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Katerina ScharovDepartment of Paediatric Oncology, Haematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Düsseldorf, Germany.
Angela Maria SavinoTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Julian Schliehe-DiecksDepartment of Paediatric Oncology, Haematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Düsseldorf, Germany.
Michela BardiniTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Grazia FazioTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Silvia BresolinPediatric Hematology, Oncology and Stem Cell Transplant Division, Women and Child Health Department, Padua University and Hospital, Padua, Italy.
Andrea BiondiSchool of Medicine and Surgery, University of Milano-Bicocca, Italy.
Arndt BorkhardtDepartment of Paediatric Oncology, Haematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Düsseldorf, Germany.
Sanil BhatiaDepartment of Paediatric Oncology, Haematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Düsseldorf, Germany.
Giovanni CazzanigaTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
Chiara PalmiTettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combining multiple drugs broadens the window of therapeutic opportunities and is crucial for diseases that are currently lacking fully curative treatments. A powerful emerging tool for selecting effective drugs and combinations is the high-throughput drug screening (HTP). The histone deacetylase inhibitor (HDACi) givinostat (ITF2357) has been shown to act effectively against CRLF2-rearranged pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), a subtype characterized by poor outcome and enriched in children with Down Syndrome, very fragile patients with a high susceptibility to treatment-related toxicity. The aim of this study is to investigate possible synergies with givinostat for these difficult-to-treat patients by performing HTP screening with a library of 174 drugs, either approved or in preclinical studies. By applying this approach to the CRLF2-r MHH-CALL-4 cell line, we identified 19 compounds with higher sensitivity in combination with givinostat compared to the single treatments. Next, the synergy between givinostat and the promising candidates was further validated in CRLF2r cell lines with a broad matrix of concentrations. The combinations with trametinib (MEKi) or venetoclax (BCL2i) were found to be the most effective and with the greatest synergy across three metrics (ZIP, HAS, Bliss). Their efficacy was confirmed in primary blasts treated

Indexed as

Combination treatmentCRLF2 rearranged acute lymphoblastic leukemiaGivinostatHigh-throughput drug screeningTrametinibVenetoclax

Identifiers

PMID39071567
PMCPMC11277435

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Registered trials

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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.