Patients with B cell lymphomas bearing MYC translocation combined with translocation involving other genes, such as BCL2, BCL3, or BCL6, defined as double-hit lymphoma (DHL), have a poor prognosis.
By FISH analysis, 19.6%, 4.6%, 26.1%, and 3.9% cases showed rearrangement at IGH, BCL2, BCL6, and MYC loci, respectively, including three (2.0%) cases of double-hit lymphoma.
Finally, inhibition of PLK1 triggered degradation of MYC and of the antiapoptotic protein MCL-1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL cell growth, survival, and tumorigenicity, supporting clinical targeting of PLK1 in DHL.
Patients with B cell lymphomas bearing MYC translocation combined with translocation involving other genes, such as BCL2, BCL3, or BCL6, defined as double-hit lymphoma (DHL), have a poor prognosis.
To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials.
The germinal center subtype patients with isolated BCL2 translocations had significantly worse outcome than the patients without BCL2 rearrangements (P=0.0002), and their outcome was similar to that of patients with the activated B-cell subtype (P=0.30), but not as bad as the outcome of patients with double hit lymphoma (P<0.0001).
Double-hit lymphoma (DHL) is a subgroup of aggressive lymphomas with both MYC and BCL2 gene rearrangements, characterised by a rapidly progressing clinical course that is refractory to aggressive treatment and short survival.
Dual translocation of MYC and BCL2 or the dual overexpression of these proteins in patients with aggressive B-cell lymphomas (termed double-hit lymphoma [DHL] and double-expressor lymphoma [DEL], respectively) have poor outcomes after chemoimmunotherapy with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare.
We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy.
Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53.
We studied the clinicopathological features and outcome of 13 patients with MYC/BCL6 DHL and compared this group to a group of 83 MYC/BCL2DHL patients.
Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare.
The correlation of EZH2 expression with aggressive behavior and proliferation rate in B-cell neoplasms suggests that this molecule may function as an oncogenic protein in these neoplasms, with possible regulation by different signaling cascades in different types of aggressive B-cell lymphomas: p-ERK-related signaling in diffuse large B-cell lymphoma, and MYC-related signaling in Burkitt lymphoma and double hit lymphoma.
We report our experience with 129 cases of double hit lymphoma (DHL), defined as B-cell lymphoma with translocations and/or extra signals involving MYC plus BCL2 and/or BCL6.
Most of the refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture.
The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma.