Described both in B-cell acute lymphoblastic leukemia (ALL) and in non-Hodgkin lymphomas (NHL), especially in Burkitt lymphoma , and double-hit diffuse large B-cell lymphomas (DLBCL).

The postulated normal counterpart is the germinal centre or post-germinal centre B-cell.

Most Burkitt lymphoma cases show the t(8;14)(q24;q32) [MYC-IGH] and less commonly the t(8;22)(q24;q11) or t(2;8)(p12;q24). The translocation is present in both the endemic African Burkitt lymphoma and in the non endemic tumor type (Europe, America, and Japan). In case the Burkitt lymphoma infiltrated the bone marrow (leukemic phase) the MYC-translocation can be demonstrated in the bone marrow or blood as well. If no immunophenotyping results are available, it is good practice to exclude a BCL2 rearrangement because a t(8;14) can be observed in other B cell neoplasms (such as double hit DLBCL see below).
Some DLBCL (double-hit) cases contain the t(8;14) translocation. In some clinical studies patients with DLBCL and MYC rearrangement will receive more aggressive treatment.
The disease defines the prognosis. Given the correct treatment regime Burkitt lymphoma patients do well, while the outcome in double-hit DLBCL patient is totally different.

ALL : L3 morphology according to the FAB classification, very occasionally L1 or L2 cytology reported.

t(8;14) is described in 75-85% of the cases, t(2;8) in 5%, and t(8 ;22) in the remaining 10%; high-quality metaphases are required to detect t(8;14) and t(8;22).

Reported in 70% cases in Burkitt lymphoma and DLBCL, especially: t(14;18)(q32;q21) in double-hit DLBCL lymphomas, structural rearrangements of the long arm of chromosome 1 (30% cases) resulting in a partial trisomy 1q, rearrangements of 13q34 (15% cases).

t(2;8)(p12;q24) and t(8;22)(q24;q11) are variants of the t(8;14)(q24;q32); three-way rearrangements and translocations of submicroscopic chromosome fragments have also been described.

No hybrid transcript. The translocation leads to the MYC gene under direct regulation of the enhancer of the IGH (or IGK/IGL genes), thereby causing high level transcription of the MYC gene .

MYC is translocated to der(14) in the t(8;14), whereas it remains on der(8) in the variant translocations; t(8;14) leads to a head-to-head fusion of MYC with the heavy chain immunogloulin locus : 8q24 is close to the 5 extremity of MYC exon 2, leading the all translated gene region to 14q32; the 8q24 breakpoint region is variable, scattered over a 190 Kb region, 5 far from MYC or within MYC; the 14q32 breakpoint region is mainly located in the constant region, very close within the switch or joining regions; MYC juxtaposed to the immunoglobin constant regions and enhancer is overexpressed, shutting down the normal remaining MYC; in both t(2;8) and t(8;22), the breakpoint is in 3 of or distal to the MYC gene which always remains on der(8); the rearrangement with respectively IGK or IGL and MYC is head-to-tail.

The protein MYC resulting from the translation of the second and third exons, through DNA- binding properties, plays a role in regulating cell growth and differentiation.

Constitutive expression of MYC induces proliferation even in the absence of growth factors

IGH/MYC

IGK/MYC

IGL/MYC

The 3 translocations are variants of each other, and they share the same clinical significance.