MALT lymphoma meets stem cells

Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct clinico-pathologic entity mainly associated with chromosomal translocations involving the MALT1 gene. Therefore, these chromosomal rearrangements have been traditionally used to identify tumor MALT lymphoma B-cells, and they have always been detected in differentiated tumoral B cells. However, the hematopoietic progenitor and stem cells (HS/PCs) seem not to show any of the translocations detected in tumor B cells, although these aberrations would be difficult to detect if the frequency of these putative stem cells harboring the translocation was low. These results would seem to suggest that the MALT lymphoma cell-of-origin, in which the oncogene activation takes place (as a result of the mentioned chromosomal rearrangement), is not a stem/progenitor cell. However, until now, all the experiments targeting the expression of human MALT1 oncogene to the mouse B-cell compartment have failed to reproduce the human disease in mice. Therefore, it is potentially possible that, in human patients, the occurrence of MALTassociated oncogenic alterations might happen in the (HS/PCs) compartment, and this cell-of-origin adopts/acquires afterwards a MALT lymphoma cell fate as a consequence of the MALT1 activity. To elucidate if MALT lymphoma is a stem cell-driven tissue, we developed mice in which we limited MALT1 expression to the Sca1 cells (Sca1-MALT1 mice). Sca1-MALT1 mice developed clonal extranodal B-cell lymphomas recapitulating not only the main clinical, histopathological and molecular features of human MALT lymphomas, but also the progression to the aggressive form of MALT lymphoma meets stem cells