Evidence map›Paper›PMID 28331226›Full record

ArticleLeukemia2017

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL.

A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K L Davis, G Gaipa and 7 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05088226 (Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute B Cell Lymphoblast Leukemia Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation), which is not on this map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.2field-weighted citation impact, top 7% 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.

NCT05088226 phase2recruitingnot on this mapstarted 2021, after this paper: background citation

Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute B Cell Lymphoblast Leukemia Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation

TypeinterventionalSponsorChinese PLA General HospitalRan2021 to 2031Enrolled50ConditionsPeripheral Blood Stem Cell TransplantationArmsRuxolitinib combined with Chidamide.
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 46 citations in OpenAlex.

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  18. Givinostat: an emerging treatment for polycythemia vera.Expert opinion on investigational drugs · 2020
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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 6 institutions in 4 countries.

A M SavinoTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
J SarnoTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
L TrentinDepartment of Women's and Children's Health, University of Padova, Padova, Italy.
M VieriTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
G FazioTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.ORCID 0000-0001-7077-8422
M BardiniTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
C BugarinTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
G FossatiPreclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy.
K L DavisBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
G GaipaTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
S IzraeliDepartment of Pediatric Hematology and Oncology, Leukemia Research Section, Edmond and Lily Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
L H MeyerDepartment of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
G P NolanBaxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
A BiondiTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
G Te KronnieDepartment of Women's and Children's Health, University of Padova, Padova, Italy.
C PalmiTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
G CazzanigaTettamanti Research Center, Department of Pediatrics, University of Milano Bicocca, Fondazione MBBM, Monza, Italy.
University of Milano-Bicocca · ITStanford Medicine · USTel Aviv University · ILUniversity of Padua · ITItalfarmaco (Italy) · ITUniversität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert anti-neoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations. Likewise, givinostat killed primary cells, but not their normal hematopoietic counterparts, from patients carrying CRLF2 rearrangements. At low doses, givinostat downregulated the expression of genes belonging to the JAK/STAT pathway and inhibited STAT5 phosphorylation. In vivo, givinostat significantly reduced engraftment of human blasts in patient-derived xenograft models of CRLF2-positive BCP-ALL. Importantly, givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications.

Indexed as

AdolescentAnimalsCarbamatesCell Line, TumorChild, PreschoolFemaleHistone Deacetylase InhibitorsHumansMaleMiceNitrilesPhosphorylationPrecursor Cell Lymphoblastic Leukemia-LymphomaPyrazolesPyrimidinesReceptors, CytokineCarbamatesCRLF2 protein, humangivinostatHistone Deacetylase InhibitorsNitrilesPyrazolesPyrimidinesReceptors, CytokineruxolitinibSTAT5 Transcription Factor

Identifiers

PMID28331226
OpenAlexW2602726122

What OpenQuestion holds

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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.