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Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

Publication ,  Journal Article
Xu-Monette, ZY; Dabaja, BS; Wang, X; Tu, M; Manyam, GC; Tzankov, A; Xia, Y; Zhang, L; Sun, R; Visco, C; Dybkaer, K; Yin, L; Chiu, A; Zu, Y ...
Published in: Mod Pathol
December 2015

MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about the tumor biology associated with MYC dysregulation is important to understand the roles of MYC and MYC-associated biology in lymphomagenesis. In this study, we determined MYC rearrangement status (n=344) and Myc expression (n=535) in a well-characterized DLBCL cohort, individually assessed the clinical and pathobiological features of patients with MYC rearrangement and Myc protein overexpression, and analyzed the prognosis and gene expression profiling signatures associated with these MYC abnormalities in germinal center B-cell-like and activated B-cell-like DLBCL. Our results showed that the prognostic importance of MYC rearrangement vs Myc overexpression is significantly different in germinal center B-cell-like vs activated B-cell-like DLBCL. In germinal center B-cell-like DLBCL, MYC-rearranged germinal center B-cell-like DLBCL patients with Myc overexpression significantly contributed to the clinical, biological, and prognostic characteristics of the overall Myc-overexpressing germinal center B-cell-like DLBCL group. In contrast, in activated B-cell-like DLBCL, the occurrence, clinical and biological features, and prognosis of Myc overexpression were independent of MYC rearrangement. High Myc levels and Myc-independent mechanisms, either tumor cell intrinsic or related to tumor microenvironment, conferred significantly worse survival to MYC-rearranged germinal center B-cell-like DLBCL patients, even among Myc(high)Bcl-2(high) DLBCL patients. This study provides new insight into the tumor biology and prognostic effects associated with MYC dysregulation and suggest that detection of both MYC translocations and evaluation of Myc and Bcl-2 expression is necessary to predict the prognosis of DLBCL patients.

Duke Scholars

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Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

December 2015

Volume

28

Issue

12

Start / End Page

1555 / 1573

Location

United States

Related Subject Headings

  • Vincristine
  • Transcriptome
  • Rituximab
  • Proto-Oncogene Proteins c-myc
  • Proportional Hazards Models
  • Prognosis
  • Prednisone
  • Pathology
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Xu-Monette, Z. Y., Dabaja, B. S., Wang, X., Tu, M., Manyam, G. C., Tzankov, A., … Young, K. H. (2015). Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Mod Pathol, 28(12), 1555–1573. https://doi.org/10.1038/modpathol.2015.118
Xu-Monette, Zijun Y., Bouthaina S. Dabaja, Xiaoxiao Wang, Meifeng Tu, Ganiraju C. Manyam, Alexander Tzankov, Yi Xia, et al. “Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.Mod Pathol 28, no. 12 (December 2015): 1555–73. https://doi.org/10.1038/modpathol.2015.118.
Xu-Monette, Zijun Y., et al. “Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.Mod Pathol, vol. 28, no. 12, Dec. 2015, pp. 1555–73. Pubmed, doi:10.1038/modpathol.2015.118.
Xu-Monette ZY, Dabaja BS, Wang X, Tu M, Manyam GC, Tzankov A, Xia Y, Zhang L, Sun R, Visco C, Dybkaer K, Yin L, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WWL, van Krieken JH, Huh J, Ponzoni M, Ferreri AJM, Møller MB, Parsons BM, Zhao X, Winter JN, Piris MA, McDonnell TJ, Miranda RN, Li Y, Medeiros LJ, Young KH. Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Mod Pathol. 2015 Dec;28(12):1555–1573.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

December 2015

Volume

28

Issue

12

Start / End Page

1555 / 1573

Location

United States

Related Subject Headings

  • Vincristine
  • Transcriptome
  • Rituximab
  • Proto-Oncogene Proteins c-myc
  • Proportional Hazards Models
  • Prognosis
  • Prednisone
  • Pathology
  • Middle Aged
  • Male