Is there a clonal relationship between leukemic cells and bone marrow mesenchymal stem cells

a , Supervisors: Monique den Boer b , Lieke van den Berk b a Abstract Despite risk-adapted therapy, 20% of children with acute lymphoblastic leukemia (ALL) do not respond well to chemotherapy. One theory states that the interaction between the leukemic cells (LCs) and the mesenchymal stem cells (MSCs) plays an important role in the pathogenesis of leukemia. Recent studies have shown that the MSCs might contain the same aberration as the ones that are found in leukemic cells. In this systematic review we compared six articles to determine if aberrations found in the LCs might also be present in MSCs and whether this shows evidence for a possible clonal relationship. Overall four articles did not detect a possible clonal relationship between the LCs and MSCs. The remaining two articles reported a clonal relationship between the LCs and BM-MSCs. To assess whether aberrations similar to those found in LCs are also present in the MSCs and to show evidence that no contamination took place, FISH, immunophenotyping and V(D)J rearrangements were performed by the researchers of the above mentioned articles. Despite their contradictory conclusions based on the V(D)J rearrangements, the two articles both indicated that there is a possible clonal relationship between MSCs and LCs. Based on this evidence, we do not think that MSCs play a crucial role in the pathogenesis of leukemia, but it is likely that a clonal relationship is present in one specific type of leukemia, MLL-AF4, which arises in utero. This conclusion must be qualified because it is still unknown whether MSCs are V(D)J positive or not. This makes contamination hard to rule out. The best way to provide evidence for a clonal relationship between MSCs and LCs would be by dual detection. The dual detection marker would contain the 'fusion gene' and a marker for ALL (CD19) or MSCs (CD105). By means of this dual detection it can be shown that the aberration would either be in ALL cells, in MSCs, or in both. This would provide conclusive evidence for contamination.