Genes associated with multi-hit DLBCL:
(1) c-MYC translocation at 8q24 (causes accelerated cell proliferation, seen in Burkitt lymphoma)
(2) BCL2 at 18q21.3 (inhibits apoptosis)
(3) BCL6 at 3q27 (causes accelerated cell proliferation)
(4) others
Common c-MYC translocations: t(8;14) (q24;q32), t(2;8) (p11;q24), t(8;22) (q24;q11)
Common BCL2 translocations: t(14;18) (q32;q21.3), t(2;18) (p11;q21.3), t(18;22) (q21.3;q11)
where:
• 14q32 has the immunoglobulin heavy chain gene (IGH).
• 2q21 has the immunoglobulin kappa light chain gene.
• 22q11 has the immunoglobulin lambda light chain gene.
Features of double or triple hit lymphomas:
(1) poor response to chemotherapy with R-CHOP
(2) advanced stage, CNS involvement and/or bone marrow involvement at presentation
(3) elevated serum LDH
(4) presence of B symptoms
(5) CD10 positive with reduced expression of CD20 and high Ki-67 proliferative index