UM171 promotes expansion of autologous peripheral blood hematopoietic stem cells from poorly mobilizing lymphoma patients.

BACKGROUND

Autologous hematopoietic stem cell transplantation is an effective therapeutic strategy for lymphoma patients. However, some patients have to give up receiving transplantation because of failing to obtain sufficient CD34 cells yields. Therefore, we ex vivo expanded HSCs of lymphoma patients using UM171 to solve the problem of HSCs deficiency.

METHODS

Mobilized peripheral blood-derived CD34 cells from lymphoma patients were cultured for 10 days with or without UM171. The fold of cell expansion and the immunophenotype of expanded cells were assessed by flow cytometry. RNA-seq experiment was performed to identify the mechanism by which UM171 promoted HSCs expansion.

RESULTS

UM171 treatment increased the proportion of CD34 (68.97 ± 6.91%), CD34 CD38 cells (44.10 ± 9.20%) and CD34CD38CD45RACD90 LT-HSCs (3.05 ± 2.08%) compared to vehicle treatment (36.08 ± 11.14%, 18.30 ± 9.49% and 0.56 ± 0.45%, respectively). UM171 treatment led to an 85.08-fold increase in LT-HSC numbers relative to initial cells. Importantly, UM171 promoted expansion of LT-HSCs achieved 138.57-fold in patients with poor mobilization. RNA-seq data showed that UM171 upregulated expression of HSC-, mast cell-specific genes and non-canonical Wnt signaling related genes, and inhibited genes expression of erythroid, megakaryocyte and inflammatory mediated chemokine.

CONCLUSIONS

Our study shows that UM171 can efficiently promote ex vivo expansion of HSCs from lymphoma patients, especially for poorly mobilizing patients. In terms of mechanism, UM171 upregulate HSC-specific genes expression and suppress erythroid and megakaryocytic differentiation, as well as activate non-classical Wnt signaling.