Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis

Abstract

Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

“…30 Gains were considered when three or four copies of the gene studied were identified, whereas more than four copies were considered as amplifications. 31 However, as we did not use a centromer probe in this study, we cannot distinguish between true polysomies and partial chromosomal gains.…”

“…Mossafa et al also reported that MYC amplification was an unfavorable alteration in a group of patients with highgrade B-lymphomas, including 12 with transformed lowgrade B-cell lymphomas and three DLBCL. 31 MYC rearrangements have been detected in 6 to 14% of de novo DLBCL. In our study, 12 (7%) cases showed MYC rearrangement and 7/12 (58%) had additional rearrangements of BCL2 and/or BCL6.…”

Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge

“…Other mechanisms such as amplification or deregulation by juxtaposition of MYC with other genes might also lead to MYC overexpression and as a result a BL-like morphology. 51,52 Non-IG-MYC translocation may occur as a secondary event (for example, in follicular lymphoma), resulting in a transformed lymphoma with a BL-like morphology. 53 Although the numbers were small, we compared the genetic profile of the 13 BL with a non-IG-MYC breakpoint with that of the core subset.…”

The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas

“…13 Nevertheless, the proper classification of a tumor as BL or DLBCL is of paramount importance, as these tumors exhibit distinct biological behaviors and are treated with different chemotherapeutic regimens. 11,[14][15][16] Recently, it has become apparent that rare cases of DLBCL lacking the morphological and/or immunophenotypic features of BL can harbor a c-MYC translocation (MYC + DLBCL). 17 These tumors respond poorly to conventional, DLBCL-based chemotherapeutic regimens and might, therefore, be considered for BL-type regimens in the future.…”