The Endosteum

Only a subset of hierarchically arranged, primitive humanAMLprogenitor cells can initiate the disease in transplanted immune-deficientmice. Apublication inNatureBiotechnologyby Ishikawaet al. (2007) describes a new animalmodel to study chemotherapy-resistant, quiescent humanAMLCD34+CD38 stem cells, which are retained in the endosteum region. Characterization of the bone marrow (BM) microenvironment supporting growth and survival of normal and malignant hematopoietic stem cells presents a major challenge. Early ob-servations revealed that bone frac-tures, blood that has just passed through bone, and trauma and injury to the endosteal milieu all provide a primitive CD34+CD38 and more dif-ferentiated, immature CD34+CD38+ populations sorted from patient sam-ples into newborn NOD/SCID/IL2rgnull immune-deficient mice. These mice are currently the most immune-defi-cient recipients and thus the most permissive for human stem cell trans-plantation and identification of serially determined that human CD34+CD38 LSCs primarily homed to and were retained in greater numbers in the end-osteum region of the femur. It has been shown previously that normal enriched primitive murine progenitor cells pref-erentially home to this site, while more committed progenitors favore