title: Diffuse large B-cell lymphoma with MYC gene rearrangements: Current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature.
abstract: In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.
authors.affiliation: VU University Medical Centre, Department of Haematology, Amsterdam, The Netherlands.
authors.forename: A V
authors.initials: AV
authors.lastname: de Jonge
authors.affiliation: VU University Medical Centre, Department of Haematology, Amsterdam, The Netherlands.
authors.forename: T J A
authors.initials: TJ
authors.lastname: Roosma
authors.affiliation: Spaarne Gasthuis, Department of Internal Medicine, Haarlem, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Houtenbos
authors.affiliation: Sint Lucas Andreas Hospital, Department of Haematology, Amsterdam, The Netherlands.
authors.forename: W L E
authors.initials: WL
authors.lastname: Vasmel
authors.affiliation: Zaans Medical Centre, Department of Internal Medicine, Zaandam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van de Hem
authors.affiliation: Netherlands Cancer Institute, Department of Medical Oncology, Amsterdam, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: de Boer
authors.affiliation: West Fries Gasthuis, Department of Internal Medicine, Hoorn, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van Maanen
authors.affiliation: Rode Kruis Hospital, Department of Internal Medicine, Beverwijk, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Lindauer-van der Werf
authors.affiliation: Spaarne Gasthuis, Department of Internal Medicine, Hoofddorp, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Beeker
authors.affiliation: Amstelland Hospital, Department of Internal Medicine, Amstelveen, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Timmers
authors.affiliation: Gelre Hospital, Department of Internal Medicine, Apeldoorn, The Netherlands.
authors.forename: C G
authors.initials: CG
authors.lastname: Schaar
authors.affiliation: Slotervaart Hospital, Department of Internal Medicine, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Soesan
authors.affiliation: VU University Medical Centre, Department of Clinical Genetics, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Poddighe
authors.affiliation: VU University Medical Centre, Department of Pathology, Amsterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: de Jong
authors.affiliation: VU University Medical Centre, Department of Haematology, Amsterdam, The Netherlands. Electronic address: m.chamuleau@vumc.nl.
authors.forename: M E D
authors.initials: ME
authors.lastname: Chamuleau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
keywords: BCL-U; BCL2; DA-EPOCH-R; DLBCL; Double hit lymphoma; MYC; R-CHOP; Single hit lymphoma; Triple hit lymphoma