Publications by authors named "Issa Ismail Issa"

Numerous clinical trials have attempted to improve first-line R-CHOP treatment of diffuse large B-cell lymphoma (DLBCL) through the addition or substitution of drugs. The REMoDL-B trial, testing the addition of bortezomib (RB-CHOP), revealed that ABC and molecular high-grade DLBCL patients benefit from bortezomib. The aim of this study was to achieve a better understanding of the bortezomib response in DLBCL through a functional investigation of clinically identified markers.

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Article Synopsis
  • High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) shares similarities with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), which complicates its diagnosis and treatment.
  • A study on a cohort of 55 patients revealed that about 60% of HGBCL, NOS cases don't express the BL gene signature and instead display characteristics aligned with DLBCL, while showing significant genetic diversity and changes in critical regulatory genes.
  • Pediatric HGBCL, NOS cases exhibited gene expressions typical of GCB-DLBCL and also showed key mutations seen in pediatric BL; the research highlighted PIM1 mutations in adults as a potential target for new therapies.
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The recurrence of diffuse large B-cell lymphoma (DLBCL) has been observed in 40% of cases. The standard of care for refractory/relapsed DLBCL (RR-DLBCL) is platinum-based treatment prior to autologous stem cell transplantation; however, the prognosis for RR-DLBCL patients remains poor. Thus, to identify genes affecting the cisplatin response in DLBCL, cisplatin-based whole-genome CRISPR-Cas9 knockout screens were performed in this study.

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Purpose: Platinum-containing therapy is standard treatment for relapsed Diffuse Large B-Cell Lymphoma (DLBCL). However, the efficacy of treatment is limited by drug resistance leading to relapse. Cisplatin resistance has been linked to impairments of the DNA damage response, and several DNA repair proteins have been identified as clients of the molecular chaperone Hsp90.

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: Bendamustine is primarily used for treatment of indolent lymphomas but has shown efficacy in some patients with diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Molecular-based patient stratification for identification of resistant patients, who will benefit from alternative treatments, is important. The aim of this study was to develop a resistance gene signature (REGS) from bendamustine dose-response assays in cultures of DLBCL and MM cell lines, enabling prediction of bendamustine response in DLBCL and MM patients.

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