Myeloid Leukaemia Factor 1 and haemopoiesis: aspects of Mlf1's regulation and function

[Truncated abstract] Myeloid Leukaemia Factor 1 (MLF1) is a putative oncogene associated with acute myeloid leukaemia. Its murine homologue, Mlf1, was independently identified as a gene up-regulated during a spontaneous in vitro erythroid-tomyeloid haemopoietic lineage switch. Ectopic Mlf1 expression in J2E erythroleukemic cells inhibits differentiation along the erythroid pathway, and induces a monocytic phenotype. Conversely, enforced expression of Mlf1 in haemopoietic progenitors and the M1 monoblastoid cell line promotes maturation along the myeloid lineage. There is a growing body of evidence to show that small, endogenous non-coding RNAs, known as microRNAs (miRNAs), play fundamental roles in many important biological processes, including haemopoiesis and leukaemia. One of the primary aims of this thesis was to investigate whether Mlf1 was a target of miRNA regulation. Indeed, it was shown that miR-29 miRNAs are capable of Mlf1 repression at both the transcript and protein levels. Furthermore, this interaction appears to be important for modulation of Mlf1 expression during differentiation of M1 cells. MLF1 is highly expressed in CD34+ haemopoietic progenitors, and its levels decline in more mature cell types. In addition, the effects of Mlf1 on haemopoietic lineage progression in vitro suggest that MLF1 has a role in early haemopoietic development and lineage commitment.