Investigating the role of extracellular Nm23-H1 protein in acute myeloid leukaemia and its functions in controlling haemopoiesis

Lilly, Andrew Joshua (2013). Investigating the role of extracellular Nm23-H1 protein in acute myeloid leukaemia and its functions in controlling haemopoiesis. University of Birmingham. Ph.D.

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Abstract

Nm23-H1 is elevated in acute myeloid leukaemia (AML) patient serum, where it is thought to enhance AML cell survival. However, the Nm23-H1 pro-survival mechanism remains poorly understood. Here it is demonstrated that AML samples are heterogeneous in their ability to bind Nm23-H1 and respond to the resultant survival signal. Although rNm23-H1 promoted the survival of the most primitive blasts within responding AMLs, it was not these cells that bound the protein. Instead, Nm23-H1 bound to more mature CD34\(^l\)\(^o\)/CD11b\(^+\)\(^v\)\(^e\) cells indicating that the survival effect on the blasts was indirect. In support of this, the survival of purified blast cells was enhanced by medium conditioned by more mature cells from the clone that had been stimulated by rNm23-H1. It is hypothesised that the AML clone subverts a signaling process between immature and more mature haemopoietic cells; a mechanism involved in controlling haemopoietic maturation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):