title: Therapeutic implication of concomitant chromosomal aberrations in patients with aggressive B-cell lymphomas.
abstract: A subset of diffuse large B-cell lymphomas (DLBCL) harbors concomitant rearrangements of MYC, BCL2 and BCL6 and is characterized by clinical aggressiveness and intrinsic refractoriness to standard chemo-immunotherapy. Commonly identified as "double or triple hit" lymphomas, these diseases represent a therapeutic challenge to chemotherapy-based regimens and likely require a more targeted approach. Herein we summarize the unique biological behavior of double and triple hit lymphomas focusing on the coordinated network of pathways that enable cancer cells to tolerate the oncogenic stress imposed by the co-expression of MYC, BCL2 and BCL6. We discuss how these enabling pathways contribute to the chemo-refractoriness of these tumors. We propose to exploit lymphoma cells' addiction to these oncogenic networks to design combinatorial treatments for this aggressive disease based on the modulation of epigenetically-silenced pathways and decreasing expression and activity of these oncogenic drivers.
authors.affiliation: a Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine , New York , NY , USA.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marullo
authors.affiliation: a Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine , New York , NY , USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Rutherford
authors.affiliation: a Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine , New York , NY , USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.affiliation: a Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine , New York , NY , USA.
authors.forename: Leandro
authors.initials: L
authors.lastname: Cerchietti
mesh_terms: D002869:Chromosome Aberrations; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D015398:Signal Transduction
keywords: BCL2 rearrangement; BCL6 rearrangement; DLBCL; Hsp90; MYC rearrangement; double-hit lymphoma; eIF4E; triple-hit lymphoma