Although HIF-1α is a positively regulated down-stream target of the PI3K/Akt/mTOR axis, HIF-1α inhibition alone could not suffice to offset the effects of an extremely enhanced PI3K/Akt/mTOR signaling with multiple other downstream targets, thus explaining the expansion failure observed in our cultured CD34+ cells of high-risk MDS patients. The gene discussed is HIF1A; the disease is myelodysplastic syndrome.