Clinical significance of 8q24/c‐MYC translocation in diffuse large B‐cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) has heterogeneous clinical, histological, and molecular features. We evaluated the clinical characteristics and prognoses of patients with DLBCL carrying 8q24 translocations. A total of 1864 consecutive patients with nonHodgkin's lymphoma were treated in the Adult Lymphoma Treatment Study Group from 1998 to 2005. Of the 252 patients with DLBCL with abnormal karyotypes, 28 patients with DLBCL with the 8q24 translocation were identified. There were 14 men and 14 women, with a median age of 61 years. The 8q24 translocation was observed significantly more frequently among patients with poor performance status, among patients with high lactate dehydrogenase level, and among patients with bone marrow involvement. The 5-year overall survival was 43.9% among the patients with 8q24 translocation, and 67% among the patients with other chromosomal abnormalities. The 8q24 translocation group showed significantly poorer prognosis than the group with other translocations. In addition, patients with t(14;18) and 8q24 translocation showed significantly poorer prognosis than those with 8q24 translocation alone. It will be necessary to study whether more aggressive chemotherapy or rituximab combination chemotherapy is effective in 8q24 translocation cases. (Cancer Sci 2009; 100: 233-237) D iffuse large B-cell lymphoma (DLBCL) accounts for approximately 50% of non-Hodgkin's lymphomas (NHL) and has heterogeneous clinical, histological, immunophenotypic, cytogenetic, and molecular features. Currently, the international prognostic index (IPI) is widely used as a prognostic factor.(1) However, it has been established that clinical features and treatment responses are also dependent on genetic and molecular features that modify disease aggressiveness. The c-MYC gene at 8q24 is involved in three translocations, most commonly t(8;14) (q24;q32), and less often t(2;8) (p12;q24) and t(8;22) (q24;q11).(2) Overexpression of c-MYC drives cell proliferation and the expression of other genes involved in cell growth.(3) C-MYC translocation is characteristic of Burkitt lymphoma; t(8;14) occurs in 80 -90% of Burkitt lymphoma cases, and in up to 5-10% of DLBCL cases.(4) C-MYC activates genes that promote cell-cycle progression and suppresses inhibitory proteins like p21CIP1 and p27KIP1.(5) Paradoxically, c-MYC also promotes apoptosis via the p19ARF-p53 apoptotic pathway.(5) c-MYC appears to be more commonly found in DLBCL with extranodal involvement and associated with a more aggressive clinical course. The relationship between 8q24/c-MYC translocation and the clinical outcome of DLBCL has been the subject of controversy. We therefore studied the clinical characteristics of DLBCL with 8q24/c-MYC translocation and correlated the findings with clinical outcome. Patients and MethodsPatients. A total of 1543 consecutive patients with NHL were treated in the Adult Lymphoma Treatment Study Group (ALTSG) in Japan from 1998 to 2005. Chromosomal data were available for 489 (58%) of the 842 patients with DLBCL. Among t...

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B‐cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab

“…13,34,35 Recently, the prognostic impact of chromosomal translocations involving MYC, BCL2, and BCL6 genes have been widely investigated in DLBCLs, but only a small number of studies have been conducted in the rituximab era (Table 3). 13,16,[19][20][21][22][23][24][25]35,38 In this study, the frequency of MYC rearrangement was 6%, which is comparable to the previous studies, which have reported in 3% to 16% of DLBCL. 13,18,[21][22][23][24][25][26][27] Several studies have analyzed the clinicopathologic presentations predicting the likelihood of MYC rearrangement.…”

“…MYC rearrangement was significantly associated with a high proliferation rate, whereas the other studies did not show any correlation between a high proliferation rate and the presence of MYC rearrangement. [21][22][23][24] In this study, MYC-rearranged DLBCLs were more frequently found in the high-risk IPI group. Barrans and colleagues found patients with MYC-rearranged DLBCL were significantly associated with an advanced stage and a higher IPI score.…”

“…21 Niitsu and colleagues showed that patients with MYC-rearranged DLBCL significantly correlated with poor performance status, bone marrow involvement, high IPI score, and elevated lactate dehydrogenase levels. 23 On the basis of these findings, one can recommend the routine screening for MYC rearrangements in DLBCL cases, with high-risk features and/or a high proliferation rate.…”

“…When treated with CHOP-like or augmented CHOP-like regimens, the 5-year survival is only 44% compared with 67% for DLBCL without a MYC aberration. 23 Furthermore, the negative impact of MYC expression supersedes the favorable prognosis of GC phenotype of DLBCL, with significantly inferior event-free survival and OS compared with either non-GC phenotype or non-MYC-associated DLBCL treated with CHOP. 22 The presence of MYC rearrangement retains its negative prognostic significance even in patients treated with rituximab and anthracycline-based immunochemotherapy, and is an independent predictor of outcome in DLBCL.…”

“…lymphoma (BL), but has also been reported to occur in DLBCLs with a frequency of 3% to 16%. 13,18,[21][22][23][24][25][26][27] Such cases have an adverse prognosis with chemoresistance and shortened survival, but little is known about the relative significance of MYC in the context of other established prognostic features. [21][22][23][24][25][26] Moreover, it is unclear whether there are identifiable clinicopathologic presentations that predict the likelihood of MYC aberrancy.…”