title: Negative impact of concurrent overexpression of MYC and BCL2 in patients with advanced diffuse large B-cell lymphoma treated with dose-intensified immunochemotherapy.
abstract: Co-expression of MYC and BCL2 proteins in diffuse large B-cell lymphoma (DLBCL), or 'double-expressor lymphoma' (DEL), results in poor patient prognosis, but the significance of DEL when aggressive treatments are applied remains uncertain. We performed a retrospective analysis of 40 patients with de novo DLBCL, who were categorized as being at high/high-intermediate risk according to the age-adjusted International Prognostic Index. Patients underwent an R-Double-CHOP regimen, a dose-intensified immunochemotherapy with or without consolidative high-dose chemotherapy followed by autologous stem cell transplantation. According to immunohistochemical analysis, 10 (25%) patients were categorized as having DEL, showing positivity for MYC (≥40%) and BCL2 (≥50%). The 3 year progression-free survival and overall survival of the DEL group were significantly worse compared with those of the non-DEL group (30% vs. 63%, p = 0.019 and 40% vs. 82%, p = 0.006, respectively). These results suggest that advanced DEL may need discrete treatment strategies.
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.|b Division of Laboratory Medicine, Department of Pathology of Microbiology , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Miura
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: c Department of Pathology , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugitani
authors.affiliation: c Department of Pathology , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Amano
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurita
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakagami
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Uchino
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kodaira
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Iriyama
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hojo
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirabayashi
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Kusuda
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.affiliation: b Division of Laboratory Medicine, Department of Pathology of Microbiology , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: a Division of Hematology and Rheumatology, Department of Medicine , Nihon University School of Medicine , Tokyo , Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Takei
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc
keywords: BCL2; MYC; diffuse large B-cell lymphoma; double-expressor lymphoma; high-dose chemotherapy