Single-cell transcriptomics in leukaemia stem cells

5th November 2018.  
Alice Giustacchini, University College London, UK

On the 5th of November 2018 Alice Giustacchini, of University College London will give a seminar entitled Single-cell transcriptomics uncovers distinct molecular signatures and dysregulated pathways in stem cells in chronic myeloid leukaemia at 2.00 pm in the College lecture theatre.  In her talk A Giustacchini will discuss the technological and scientific advances enable by single cell analysis of leukaemia cells and how these data may help reconstructing the somatic evolution of individual cancers.  Tumour progession is a crucial area of research in cancer biology with a major impact on future therapies including, notably, precision or personalised approaches to cure. All College students are invited to attend, especially those reading Medicine, Biology, Biotechnology and Pharmaceutical Sciences. The poster of the lecture can be downloaded here.

Molecularly targeted therapies can frequently induce remission in cancer, but can rarely achieve complete disease eradication, with resulting risk of disease relapse and progression. Chronic myeloid leukemia (CML) is a good example of this, with rare, propagating stem cells (SCs) that are incompletely eradicated by BCR-ABL-directed tyrosine kinase inhibitors (TKIs). Multiple lines of evidence support that CML-SCs are selectively resistant to TKI therapy, leading to disease relapse following treatment discontinuation. A better characterization of the biological pathways sustaining therapy resistance in CML-SCs is crucial for the development of new therapeutic strategies to achieve disease eradication. However, it has proven challenging to characterize this clinically relevant population of CML-SCs, as they reside in the same immunophenotypic compartment as the normal hematopoietic stem cells (HSCs), from which they cannot be reliably distinguished. To this aim, we developed a novel method that allows for simultane­ous single-cell RNA sequencing and high-sensitivity, targeted muta­tion detection. The unprecedented resolution on CML-SCs that our analysis achieved allowed for the characterization of distinct molecular signatures of CML-SCs from diagnosis through remission and disease progression, with potential implication for future refinement of targeted therapies in CML.

[1] Giustacchini A, Thongjuea S, Barkas N, Woll PS, Povinelli BJ, Booth CAG, Sopp P, Norfo R, Rodriguez-Meira A, Ashley N, Jamieson L, Vyas P, Anderson K, Segerstolpe Å, Qian H, Olsson-Strömberg U, Mustjoki S, Sandberg R, Jacobsen SEW, Mead AJ. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nature Medicine. 2017.  2017 Jun;23(6):692-702.

[2] Nucera S*, Giustacchini A*, Boccalatte F, Calabria A, Fanciullo C, Plati T, Ranghetti A, Garcia-Manteiga J, Cittaro D, Benedicenti F, Lechman ER, Dick JE, Ponzoni M, Ciceri F, Montini E, Gentner B, Naldini L. *first co-author. miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia. Cancer Cell. 2016 June 13;29(6):905-21.

Alice Giustacchini obtained her PhD from San Raffaele University in 2013, under the supervision of Prof. Luigi Naldini, with a project focusing on the role of microRNAs in the regulation of hematopoietic stem cell functions. Later in 2013, she moved to the UK to undertake a post-doctoral project in the laboratory of Prof. Sten Eirik Jacobsen at the University of Oxford. During her post-doc she focused on the development of novel single-cell approaches to resolve cell heterogeneity in leukemic stem cells during therapy response. Since 2017 she joined University College London where she is leading her own group focusing on the characterization of metabolic heterogeneity in myeloid leukemia stem cells and its implication for therapy response.

Leukaemic cells under the microscope.

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