// Laurie Herviou 2 , Giacomo Cavalli 2 , Guillaume Cartron 3,4 , Bernard Klein 1,2,3 and Jérôme Moreaux 1,2,3 1 Department of Biological Hematology, CHU Montpellier, Montpellier, France 2 Institute of Human Genetics, CNRS UPR1142, Montpellier, France 3 University of Montpellier 1, UFR de Médecine, Montpellier, France 4 Department of Clinical Hematology, CHU Montpellier, Montpellier, France Correspondence to: Jérôme Moreaux, email: // Keywords : hematological malignancies, EZH2, Polycomb complex, therapeutic target Received : August 07, 2015 Accepted : October 14, 2015 Published : October 20, 2015 Abstract Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies.

Hematologic Neoplasms

Hematological Malignancy

10.18632/oncotarget.6198

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Targeting Transcription-Replication Conflicts using G-quadruplexes stabilizers in Multiple Myeloma

Deleted Journal (2025)

Laure Dutrieux Sara Ovejero Antoine Guillemin Leriem ZELLAGUI Elke De BRUYNE

Replication

Transcription

G-quadruplex

10.1016/j.bneo.2025.100072

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ROLE OF UP‐FRONT AUTOLOGOUS STEM CELL TRANSPLANTATION IN PERIPHERAL T‐CELL LYMPHOMAS: a PROPENSITY SCORE MATCHING ANALYSIS OF PATIENTS FROM LYSA CENTERS

Hematological Oncology (2017)

Gaëlle Fossard Florence Broussais Inês Coelho Sébastien Bailly Emmanuelle Nicolas‐Virelizier

Introduction: Despite years of attempts to improve the prognosis of patients, peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding the type of first-line treatment. The benefit of autologous stem cell transplant (ASCT) as a consolidation procedure for patient in partial or complete response (PR or CR) is still intensely debated. Methods: Patient age, disease severity, and induction regimen are known potential confounding factors undermining the formal assessment of ASCT in first-line settings. Moreover, no retrospective study has focused on patients in response after induction, leading to strong bias in favor of the consolidation procedure. In the absence of randomized trials addressing the role of ASCT, we used a Cox proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not allocated to ASCT in intention-to-treat. Among 527 patients with peripheral PTCL-NOS, AITL or ALK- ALCL screened from 14 centers in France, Belgium, and Portugal, a final cohort of 269 patients with partial or complete responses after induction was identified and information about treatment allocation was carefully collected before therapy initiation. Results: With a median follow-up of 5.3 years, the median PFS was 3.7 years, and the median OS was 8.4 years for the entire cohort. At 5 years, PFS was 45.0% (95% confidence interval (CI): 37.8-50.6%), and OS was 60.4% (95% CI: 53.6-66.5%). Patients with ALK- ALCL experienced a slightly longer time to progression compared to patients with PTCL-NOS or AITL, although the difference did not reach significant difference. No OS difference was observed according to histology subtype. Multivariate analysis demonstrated that only remission status (CR vs. PR) at the end of induction was associated with significantly prolonged PFS and OS. In the final matched population of 146 patients, no difference regarding progression-free survival (PFS) or overall survival (OS) was observed (P = .33 and P = .40). No difference according to the use of up-front ASCT in ITT was further noted when patients with advanced stage disease (III or IV), with aaIPI > 1 or reaching a PR only at the end of induction were considered (data not shown). Conclusion: The present data do not support the use of ASCT for up-front consolidation for patients with PTCL-NOS, AITL or ALK- ALCL with partial or complete response after induction. Keywords: autologous stem cell transplantation (ASCT); peripheral T-cell lymphomas (PTCL).

Peripheral T-cell lymphoma

Autologous stem-cell transplantation

10.1002/hon.2437_64

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Patient-Reported Outcomes (PROs) from the Phase 2 TRANSCEND FL Study of Lisocabtagene Maraleucel (liso-cel) in Patients (pts) with Relapsed or Refractory Follicular Lymphoma (FL)

Blood (2023)

Guillaume Cartron Alejandro Martı́n Juan Luís Reguera Saurabh Dahiya Shien Guo

Follicular lymphoma

Refractory (planetary science)

10.1182/blood-2023-180175

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Translation Inhibition through eIF4A1 Targeting in Multiple Myeloma Is a Promising Therapeutic Strategy

Blood (2023)

Laure Dutrieux Elle Loughran Armelle Choquet Hélène Herault Antoine Guillemin

EIF4A1

Ixazomib

10.1182/blood-2023-184749

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Follicular lymphoma prognostic factors in the modern era: what is clinically meaningful?

International Journal of Hematology (2010)

Ph. Solal-Céligny Xavier Cahu Guillaume Cartron

Follicular lymphoma

Hematology

International Prognostic Index

10.1007/s12185-010-0674-x

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Citations (36)

Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Laurie Herviou Fanny Izard Ouissem Karmous-Gadacha Claire Gourzonès Céline Bellanger

SUMMARY Multiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. Here we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for histone H4K20 mono-methylation, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Remarkably, primary malignant plasma cells are particularly addicted to SETD8 activity. Indeed, pharmacological inhibition of this enzyme by the chemical compound UNC0379 demonstrated a significantly higher toxicity in MM cells compared to normal cells from the bone marrow microenvironment. Moreover, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and an activation of the p53 canonical pathway, which together leads to an impairment of myeloma cell proliferation and survival. However, UNC0379 treatment triggers a deadly level of replicative stress in p53 deficient MM cells, indicating that the cytotoxicity associated with SETD8 inhibition is independent of the p53 status. Consistent with this, the combination of UNC0379 with the conventional cytotoxic agent melphalan strongly enhances DNA damage and overcomes drug resistance in myeloma cells. Thus, targeting SETD8 could be of therapeutic interest to improve MM treatment in high-risk patients independently of the p53 status.

Melphalan

10.1101/776930

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Citations (1)