Establishment and characterization of a MALT lymphoma cell line carrying an API2‐MALT1 translocation

• Published in: Genes chromosomes & cancer Vol. 59; no. 9; pp. 517 - 524
• Main Authors: Izumi, Kiyotaka, Nishikori, Momoko, Yuan, Hepei, Otsuka, Yasuyuki, Nakao, Kensuke, Takaori‐Kondo, Akifumi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-09-2020; Wiley Subscription Services, Inc
• Subjects: API2‐MALT1; Apoptosis; cell line; Chromosome translocations; Endoplasmic reticulum; Genetic transformation; Heavy chains; Immunoglobulins; Intestine; Lymphoma; MALT lymphoma; MALT1 inhibitor; microarray analysis; Mucosal-associated lymphoid tissue; Myc protein; Polymerase chain reaction; Tumor cell lines; MALT lymphoma; microarray analysis; API2-MALT1; cell line; MALT1 inhibitor
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.22855

MALT lymphomas with API2(BIRC3)‐MALT1 translocation usually have an indolent clinical course and rarely transform into aggressive lymphoma, and there have been no lymphoma cell lines carrying API2‐MALT1 translocation reported to date. We established a novel lymphoma cell line named BMA19, carrying the API2‐MALT1 translocation from a patient with histologic transformation of intestinal MALT lymphoma. The cells were suggested to carry API2‐MALT1 and MYC‐IGH translocations by chromosomal analysis, and these translocations were confirmed by polymerase chain reaction analysis. The expression of MYC was shown to be enhanced as a result of the MYC‐IGH translocation, and it is considered to have played a role in the histologic transformation of MALT lymphoma. Whole exome sequencing of BMA19 identified several nucleotide variations in genes reported to be mutated in previous studies of marginal zone lymphomas. The MALT1 inhibitor MI‐2 specifically decreased cell growth, and the BMA19 cell line was suggested to be still dependent on the API2‐MALT1 signal. Subtractive microarray analysis showed that one of the earliest events resulting from MALT1 inhibition is increased susceptibility to endoplasmic reticulum stress‐induced apoptosis. The BMA19 cell line is considered to conserve the biological properties of MALT lymphoma and is expected to be a valuable tool for research into the pathogenesis of MALT lymphoma with an API2‐MALT1 translocation.