Presence of somatic hypermutation and activation-induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21)

Aim: Acute lymphoblastic leukemia (ALL) with L2 (FAB) morphology has rarely been reported to show t(14;18)(q32;q21). We aimed to delineate the stage at which this type of ALL is derived in B-lineage differentiation. Methods: The somatic hypermutation (SHM) of the variable region of immunoglobulin heavy chain (IgV(H)) gene and the expression of terminal deoxynucleotidyl transferase (TdT), recombination-activating gene 1 and 2 (RAG-1 and -2), and activation-induced cytidine deaminase (AID) were investigated in three cell lines and two fresh samples, including a pair of matched fresh and cell line cells. Results: TdT, RAG-1, and RAG-2 were variably expressed. AID was expressed in four of five samples. SHM of the IgV(H) gene was found in all samples with high average frequency (11.84%) comparable with that in follicular lymphoma. Ongoing mutation was seen in two fresh samples. Conclusion: As AID and SHM are generally regarded as properties exhibited by mature B cells, the presence of AID and SHM in this study seems to be incompatible with the general understanding of the early stage derivation of ALL in B-lineage differentiation. The results here give some insight into the relationship between disease type (ALL or lymphoma) and derivation stage, the overlapping of the early stage phenotype and the mature genomic characteristics, and the probable relationship between the mechanism of the occurrence of t(14;18)(q32;q21) and the machinery causing SHM.