The human bone marrow (BM) niche in acute leukaemia

Introduction:

Poor viability of primary leukaemia cells ex vivo is a major impediment in studying cancer interactions directly with the complex multicellular human BM niche. We have optimised an advanced solution that facilitates the study of primary ALL communications with human BM cells. A range of primograft and primary ALL blasts were cultured on human BM mesenchymal stem cells^{1 – 3}. Long-term expansion of ALL cells compromised neither feeder dependence nor cancer initiating ability in immunocompromised mice. Genetic barcoding demonstrated long-term preservation of clonal composition at varying barcoding complexities.

Results:

We are adapting our ex vivo approach to include primary AML cells and CD34+ haematopoietic cells. Through stem cell genetic engineering we have derived BM-iPSC as a standardised source of the endosteal and vascular niche cells. Single-cell deep phenotyping and high throughput cytokine arrays will decipher the different constituents of the BM stem-cell hierarchy. Furthermore we are developing cell fate mapping of both BM-MSC and ALL blasts through live-cell barcoding which will allow us to track both “niche” and cancer cells particularly in response to drug combinations.

Conclusion:

We hereby describe a novel approach to investigate dynamic niche-cancer signalling networks controlling leukaemia cell survival and proliferation in the human BM.

References:

[1] Bomken S, et al. Leukemia 2013; 27(3):

718 – 721.

[2] Pal D, et al. Leukemia 2016 Aug; 30(8):

1691 – 1700.

[3] Weiland J, et al. Leukemia 2016 Sep; 30(9):

1920 – 1923.

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