(A) A decrease in osteoblast numbers in mostly untreated AML/MDS patients is shown. In a DTA_osb animal model where osteoblasts were deleted, there was a threefold increase in disease burden in addition to an alteration of lineage determination. (B) Conversely, increasing osteoblast numbers through the use of a Tph-1 inhibitor, LP533401, resumed normal hematopoiesis and resulted in a decrease of disease burden translated by a prolonged survival of leukemic mice.