Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease

Xenograft models of chronic phase human chronic myeloid leukemia (CML) have been difficult to develop because of the persistence of normal hematopoietic stem cells in most chronic phase CML patients and the lack of methods to selectively isolate the rarer CML stem cells. To circumvent this problem, we first identified nine patients' samples in which the long-term culture-initiating cells were predominantly leukemic and then transplanted cells from these samples into sublethally irradiated NOD/SCID and NOD/SCID- beta2microglobulin(-/-) mice. This resulted in the consistent and durable ( 45 months) repopulation of both host genotypes with similar numbers of BCR-ABL(+)/ Ph+ cells. The regenerated leukemic cells included an initial, transient population derived from CD34(+)CD38(+) cells as well as more sustained populations derived from CD34(+)CD38(-) progenitors, indicative of a hierarchy of transplantable leukemic cells. Analysis of the phenotypes produced revealed a reduced output of B-lineage cells, enhanced myelopoiesis with excessive production of erythroid and megakaropoietic cells and the generation of primitive (CD34(+)) leukemic cells displaying an autocrine IL-3 and G-CSF phenotype, all characteristics of primary CML cells. These findings demonstrate the validity of this xenograft model of chronic phase human CML, which should enable future investigation of disease pathogenesis and new approaches to therapy

Crystal chemistry and selected physical properties of inorganic fluorides and oxide-fluorides

importance in the development of many new technologies, andare impacting various key points of modern life, that is, energyproduction and storage, microelectronics and photonics,catalysis, automotive, building, etc. Many research fields andapplications are indeed concerned by a better knowledge of therelationships occurring between the structure of suchcompounds and some pertinent physical properties. ThisReview deals with the structural chemistry of solid-stateinorganic fluorides and oxide-fluorides, mostly transitionmetal-based, including rare-earth elements. Such a Review hasnot been published for a long time.1 Articles that recentlyappeared on inorganic fluorinated compounds were mostlyfocused on material science characteristics: morphology, surfacefunctionalization, nanostructuration of the materials andapplications, rather than on the description of characteristicstructural features.2−5 Detailed reviews focused on rare earthbasedinorganic fluorides have also appeared some yearsago..