Identification of a prospective marker for JAK2 V617F mutant cells from patients with myeloproliferative neoplasms and characterisation of haematopoietic stem cell heterogeneity.

Prick, J. (Janine) (2014) Identification of a prospective marker for JAK2 V617F mutant cells from patients with myeloproliferative neoplasms and characterisation of haematopoietic stem cell heterogeneity. thesis, Medicine.

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Abstract

The myeloproliferative neoplasms (MPNs), including polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis (MF), are clonal disorders originating from a mutation or series of mutations in haematopoietic stem and progenitor cells. In 2005, a unique gain of function mutation was discovered in a substantial proportion of MPN patients, called JAK2 V617F. In addition, the majority of JAK2 V617F negative MPN patients have recently been shown to carry a somatic mutation in CALR. The first part of this study focuses on the identification of prospective markers of JAK2 V617F mutant primitive cells from patients’ blood samples with the goal of expanding the tools available to study mutant HSCs. Using a large cell surface marker screen, twenty putative candidates have been selected and seven of them are further explored by means of sequencing colonies from additional patients’ blood samples for their JAK2 status. Three of the seven initial candidates were excluded based on inconsistent sequencing patterns, which means that they are not JAK2 specific, but the other four continue to look promising. The second part of this study evaluates normal HSC heterogeneity in both a short-term as well as a long-term clonal assay. Differences in clone size and the time of cell appearance have been shown to be able to define distinct subpopulations of primitive haematopoietic cells. This work will enable specific selection of the most primitive HSC subsets in future projects.

Item Type:	Thesis (Thesis)
Supervisor name:	Haan, Prof. Dr. Gerald de and Son, Prof. Dr. Willem van
Supervisor name:	Green, Anthony R. and Kent, Dr. David and University of Cambridge
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:47
Last Modified:	25 Jun 2020 10:47
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/817

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