Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-kappaB pathway.
We have recently shown that nuclear translocation of Bcl10 is a specific molecular determinant of Helicobacter pylori-independent mucosa-associated lymphoid tissue lymphoma (Kuo, S.-H., Chen, L. T., Yeh, K.-H., Wu, M. S., Hsu, H. C., Yeh, P. Y., Mao, T. L., Chen, C. L., Doong, S. L., Lin, J. T., and Cheng, A.-L. (2004) J. Clin.Oncol.22, 3491-3497).
The Bcl10 gene has recently been cloned from the chromosomal translocation t(1:14) (p22; q32) in a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and was implicated in the pathogenesis of this and several other tumor types.
Mutations within the BCL10 coding region resulting in truncated BCL10 proteins with loss of their proapoptotic function and preservation of their NF-kappaB activating function were detected in MALT lymphoma.
The occurrence of genomic BCL10 mutations in 35 gastric MALT-type lymphomas with or without t(11;18)(q21;q21) (10 and 25 cases, respectively) was investigated.
Three distinct chromosomal translocations, t(11;18), t(1;14), and t(14;18), involving the API2-MALT1 fusion protein, BCL10, and MALT1 have been convincingly implicated in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas.
Another gene involved in the regulation of apoptosis, the BCL10 gene, has been cloned from a MALT lymphoma cytogenetically characterized by the t(1;14)(p22;q32).
We therefore screened 51 cases of pulmonary MALT lymphoma for API2-MALT1 fusion, and studied its relationship with clinicopathologic factors including the immunohistochemical expression of BCL10, another MALT lymphoma-associated molecule.
As we observed MALT1-API2 to be an efficient target of its own E3 ubiquitin ligase activity, our data suggest that this inherent instability of MALT1-API2 prevents its accumulation and renders a potential effect on MALT lymphoma development via destabilization of BCL10 unlikely.
We assessed the incidence and clinical significance of the MALT lymphoma-associated genetic abnormalities t(11;18)/API2-MALT1, t(1;14)/BCL10-IGH, t(14;18)/IGH-MALT1, t(3;14)/FOXP1-IGH, and extra copies of MALT1 and FOXP1 in gastric MALT lymphomas from Japan.
Taken together these results support the hypothesis that enhanced BCL10 expression caused by translocation to the IGH locus can promote formation of MALT lymphomas.
Similarly, the three MALT lymphoma associated chromosome translocations, namely t(1;14)(p22;q32)/BCL10-IGH, t(14;18)(q32;q21)/IGH-MALT1,and t(11;18)(q21;q21)/BIRC3 (API2)-MALT1, are also capable of activating both canonical and non-canonical NF-κB pathways.
We investigated the efficacy of H. pylori eradication and assessed the predictive value of BCL10 nuclear expression and t(11;18)(q21;q21) regarding resistance to H. pylori eradication in primary gastric mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients from mainland China.
Our results showed five key findings, which are (a) higher detection rates of t(11;18) (21.13%) in Chinese patients with transformed MALT lymphoma, (b) lower detection rates of t(11;18) in stomach MALT lymphoma, (c) different organ localizations of MALT lymphoma in Chinese patients, (d) higher nuclear expression rates of Bcl-10 in low grade MALT (51.72%), and (e) lower response rates (50% CR, and 50% PR) to anti-H.-pylori therapy.
We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT).
The intracellular pro-apoptotic molecule bcl-10 is frequently mutated in mucosa-associated lymphoid tissue (MALT) lymphomas and various non-hematologic malignancies.