Evidence map›Paper›PMID 34771616›Full record

ArticleCancers2021

Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia.

Federica Frezzato, Andrea Visentin, Filippo Severin, Serena Pizzo, Edoardo Ruggeri, Nayla Mouawad, Leonardo Martinello, Elisa Pagnin, Valentina Trimarco, Alessia Tonini and 8 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. 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
0.8field-weighted citation impact, top 33% 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, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. 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

18 authors at 1 institution in 1 country.

Federica FrezzatoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0001-7093-2493
Andrea VisentinDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0003-0271-7200
Filippo SeverinDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0001-8712-9656
Serena PizzoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Edoardo RuggeriDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0002-9439-4121
Nayla MouawadDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Leonardo MartinelloDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0003-0877-1099
Elisa PagninDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0002-9535-0526
Valentina TrimarcoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Alessia ToniniDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Samuela CarraroDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Stefano PravatoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.
Silvia ImbergamoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0003-4748-2601
Sabrina ManniDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0001-6804-0680
Francesco PiazzaDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0002-2831-623X
Anna Maria BrunatiDepartment of Molecular Medicine, Padua University, 35121 Padua, Italy.
Monica FaccoDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0003-0100-5789
Livio TrentinDepartment of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, 35128 Padua, Italy.ORCID 0000-0003-1222-6149
University of Padua · IT

Funding

Associazione Italiana Contro le Leucemie - Linfomi e Mieloma N/AAssociazione Italiana per la Ricerca sul Cancro IG-25024Janssen Research and Development #IBR-I-17-GBL-009-V01Ricerca per Credere nella Vita (RCV); Padua, Italy. AV Fellowships
6 · The paper itself

Abstract

The Btk inhibitor ibrutinib has significantly changed the management of chronic lymphocytic leukemia (CLL) patients. Despite its clinical efficacy, relapses occur, and outcomes after ibrutinib failure are poor. Although BTK and PLCγ2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations. The heat shock protein of 70 kDa (HSP70) and its transcription factor heat shock factor 1 (HSF1) play a role in mediating the survival and progression of CLL, as well as taking part in drug resistance in various cancers. We demonstrated that resveratrol and related phenols were able to induce apoptosis in vitro in leukemic cells from CLL untreated patients by acting on the HSP70/HSF1 axis. The same was achieved in cells recovered from 13 CLL patients failing in vivo ibrutinib treatment. HSP70 and HSF1 levels decreased following in vitro treatment, correlating to apoptosis induction. We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients. The targeting of HSP70/HSF1 axis could represent a novel rational therapeutic strategy for CLL, also for relapsing patients.

Indexed as

chronic lymphocytic leukemiadrug-resistanceHSF1HSP70Ibrutinibphenols

Identifiers

PMID34771616
PMCPMC8582437
OpenAlexW3210574806

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.