Investigating the role of the microenvironment in acute myeloid leukemia initiation and chemoresistance

Key information

Application close date
07 February 2023, 11:59 GMT
Hours per week
36 (full time)
Application guidance
Posted 22 December 2022

Research topics

Cell Biology Signalling & Oncogenes Stem Cells
Background texture taken from the lab imagery.

This is a summer student position supervised by Steven Ngo from Dominique Bonnet's lab.  
 

Introduction to the Science

Acute myeloid leukemia (AML) is the most common acute leukemia diagnosed in adults, with a 5-year survival rate of less than 25%. This is largely due to the aggressive nature of AML, but also due to the gradual development of resistance to first-line treatment such as chemotherapy. AML is caused by genetic mutations acquired by the haematopoietic stem and progenitor cell (HSPC) compartment, leading to the transformation of the HSPCs into highly proliferative blasts. Similar to normal blood cell development, immature leukemic blasts can undergo partial differentiation and give rise to mature-like cells. Whilst leukemia-initiating capacity has traditionally been thought to remain exclusively in the immature compartment, there is growing evidence to suggest that the mature subfraction (bulk cells) may also contribute to the development of AML, potentially through its manipulation of the local bone marrow microenvironment.

 

About the Project

Here in the Bonnet lab, we are interested in investigating crosstalk between the leukemic cell and bone marrow microenvironment. Specifically, we are interested in how this interaction may contribute to leukemic cells’ disease propagating capacity, or to the development of resistance in response to chemotherapy. This project will involve the use of a unique human AML cell line (AML227) that contains both an immature and mature leukemic subfraction. Using this cell line, the student will investigate how each subfraction may interact with bone marrow microenvironment-derived cells (mesenchymal stromal cells) in vitro. This project will also  investigate how each subfraction responds to chemotherapy in vitro, and whether changes in the supportive stromal cells can convey chemoresistance to AML-derived subpopulations.

 

About you

This project will suit candidates studying biomedical science or medicine who have a particular interest in the tumour cell microenvironment and the cross-talk between leukemic cells and their local niche.

 

References

1.         Batsivari, A., Grey, W. and Bonnet, D. (2021)

            Understanding of the crosstalk between normal residual hematopoietic stem cells and the leukemic niche in acute myeloid leukemia.

            Experimental Hematology 95: 23-30. PubMed abstract

2.         van Galen, P., Hovestadt, V., Wadsworth II, M.H., Hughes, T.K., Griffin, G.K., Battaglia, S., . . . Bernstein, B.E. (2019)

            Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity.

            Cell 176: 1265-1281.e1224. PubMed abstract