Some diffuse large B-cell lymphomas (DLBCL) have 2 or 3 high-risk genetic mutations. These tumors tend to have a more aggressive behavior with poor survival. These are said to be double or triple hit lymphomas depending on the number of mutations present.


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)



• 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


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