Establishment of a novel MALT lymphoma cell line, ma‐1, from a patient with t(14;18)(q32;q21)‐positive Helicobacter Pylori‐Independent Gastric MALT Lymphoma

Abstract

Although t(11;18)(q21;q21), t(1;14)(p22;q32), and a few other genetic mutations are specific markers for the Helicobacter pylori (HP)-independent status of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the molecular mechanisms responsible for HP-independence of gastric MALT lymphoma without such translocations and mutations remain uncharacterized. In the present study, we describe the establishment and characterization of a novel MALT lymphoma cell line, MA-1, which was derived from a gastric MALT lymphoma which was negative for both t(11;18)(q21;q21) and t(1;14)(p22;q32); the patient had failed HP eradication therapy and chemotherapy. The cell morphology and the immunophenotype of this cell line were similar to that of the original gastric MALT lymphoma. Comparative genomic hybridization analysis showed no significant gene copy number changes. Spectral karyotyping displayed a near-diploid chromosome content (48 < 2n>XY), with at least 13 chromosome structural abnormalities. Furthermore, fluorescence in situ hybridization analyses disclosed the existence of three sub-clones, characterized by t(14;18)(q32;q21)/IGH-BCL2, t(14;18)(q32;q21)/IGH-MALT1, and the presence of both chromosomal translocations in the same cell, respectively; whereas amplification of the genes CRAD9, TRAF2, and BCL10 were not found. In conclusion, we have established the first human gastric MALT lymphoma cell line, which is characterized by unusual and complex chromosome translocations and will be useful to explore further the molecular mechanisms of HP-independence in gastric MALT lymphoma.

No evidence of IGH‐MALT1‐translocation in the Ma‐1 cell line–A reply

“…Indeed, the possibility of follicular lymphoma in the present case was excluded by extensive histological and immunohistochemical studies: (1) the histological pattern of the lymphoma cells from the neck lymph node (small lymphoid cells mainly distributed in marginal zone) and Waldeyer's ring (centrocyte-like cells and prominent lymphoepithelial lesions) was identical to the lymphoma originally found in the stomach; (2) lack of the follicular-cell lymphoma-specific germinal cell markers CD10 or BCL6 in all clinical samples and MA-1 cells. Although the authors disagree with our findings that t(14;18)(q32;q21)/IGH-MALT1 and t(14;18)(q32;q21)/IGH-BCL2 coexist in MA-1 cells (Kuo et al, 2011), karyotypic analysis of the MA-1 cell line via G-banding and SKY showed multiple structural abnormalities with at least 13 alterations identified. Thus, the better description of the karyotype of translocation of MA-1 is ''der(14)t(14;18) (q32;q21).''…”

“…In their correspondence, Flossbach et al have performed cytogenetic investigations (G-banding, CGH, FISH, and M-FISH) on the MALT-lymphoma cell line, MA-1, developed by Kuo et al (2011). The authors demonstrated largely the same karyotypic findings as published by Kuo et al (2011).…”

“…We thank Flossbach et al for their comments on our article, entitled ''Establishment of a novel MALT lymphoma cell Line, Ma-1, from a patient with t(14;18)(q32;q21)-positive Helicobacter pylori-independent gastric MALT lymphoma'' (Kuo et al, 2011). In their correspondence, Flossbach et al have performed cytogenetic investigations (G-banding, CGH, FISH, and M-FISH) on the MALT-lymphoma cell line, MA-1, developed by Kuo et al (2011).…”

“…The nomenclature should be interpreted as major finding of the fusion being located on chromosome 14, not on the balanced translocation as mentioned by the authors. Although the term ''t(14;18)'' was sometimes used in the text by Kuo et al (2011), it only reflected the existence of a translocated chromosome, a nomenclature commonly accepted in the literature to describe lymphoma. In addition, as described by Streubel et al (2003) there are not only balanced t(14;18)(q32;q21) translocations observed but also unbalanced translocations with IGH-MALT1.…”

“…In their correspondence, Flossbach et al have performed cytogenetic investigations (G-banding, CGH, FISH, and M-FISH) on the MALT-lymphoma cell line, MA-1, developed by Kuo et al (2011). The authors demonstrated largely the same karyotypic findings as published by Kuo et al (2011). However, the authors found the presence of an IGH-BCL2 translocation and the absence of a classical IGH-MALT1 translocation in MA-1, and suggested that MA-1 may not be a typical cell line for MALT lymphoma.…”