15-fold increase in the amount of committed progenitor cells in the bone marrow, indicating that overexpressed HOXA9 induces expansion of the HSC population without disrupting differentiation. From these results, it appears that HOXA9 is important in maintaining HSC populations, as well as guiding their differentiation, especially towards myeloid (erythroid and granulocyte) lineages. Expression in adult, fetal and embryonic stages Throughout the development of a mammal, there are three distinct stages of erythrocyte formation – embryonic, fetal and adult. Adult erythrocytes are the most common blood cell type in mammals, and their characteristic biconcave shape, 7-8 µm diameter and enucleation are amongst the greatest commonalities between mammalian species. However, primitive and fetal erythrocytes, which circulate during early stages of development, are markedly different from their adult counterparts, most obviously through their larger size, shorter lifespan, nucleation, containment of different hemoglobin chains, and higher oxygen affinity. The reasons for and functions of these differences are not well established. HOXA9 is a candidate for one of the genes responsible for these morphological differences between the erythrocyte lineages, as it is expressed differently in each lineage. In primitive erythrocyte precursors, HOXA9 expression is almost zero. It increases slightly in the fetal stage, and then it is expressed highly in the adult erythrocyte precursors. This expression profile links to the importance of HOXA9 in the HSC, as it mirrors the fact that HSCs are absent in the developing embryo, undergoing initial production in the fetal stage, and are vital in the adult. Furthermore, in the fetal and adult precursors, not all precursor stages display HOXA9 expression. Most of the expression is in the proerythroblast (P) stage, and a minor amount in the basophilic erythroblast (B) stage. There is almost zero expression in the orthonormoblast (O) and reticulocyte (R) stages. P and B are the first two stages of committed differentiation in the erythrocyte lineage, and this implies that HOXA9 may only be involved in the differentiation and proliferation of HSCs, rather than the erythrocyte maturation process. Clinical significance Role in acute myeloid leukemia Ordinarily, HOXA9 is expressed on chromosome 7 and the nucleoporin gene NUP98 is expressed on chromosome 11. However, a gene translocation which sometimes occurs in humans moves NUP98 onto chromosome 7, where it fuses with HOXA9 to form the NUP98-HOXA9 oncogene. This oncogene has been widely implicated in acute myeloid leukemia (AML), and expression of this oncogene is the single most highly