Title

Role of Spy1 in hematopoiesis: Implications for blood malignancies

Date of Award

2013

Degree Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

First Advisor

Lisa A. Porter

Keywords

Molecular biology, Cellular biology, Oncology

Rights

CC BY-NC-ND 4.0

Abstract

In blood malignancies, the balance of hematopoietic stem cell (HSC) self-renewal and differentiation is disturbed such that HSCs produce abnormal cells with an increased capacity to proliferate; however, the exact causes of this imbalance are not known. SpeedyA1 (Spy1) is a positive cell cycle regulator known to enhance cellular proliferation by direct binding and activation of Cyclin-dependent kinase (Cdk) Cdk2 and by promoting degradation of the Cdk inhibitor (CKI) p27 Kip1 . I demonstrate that Spy1 expression levels are elevated in early stem and progenitor cells during hematopoiesis, but that Spy1 may also be implicated in later stages of myeloid differentiation. Spy1 protein was elevated in human bone marrow tumour samples and Spy1 knock-down in HL-60 cells led to decreased cell growth as well as expression of leukemic stem cell (LSC) markers. Together, these findings demonstrate a potential role for Spy1 in regulating HSC fate and in the development of blood malignancies.