Acute myelogenous leukemia (AML) is the most common adult leukemia, characterized by the clonal expansion of immature myeloblasts initiating from rare leukemic stem (LS) cells. To understand the functional properties of human LS cells, we developed a primary human AML xenotransplantation model using newborn nonobese diabetic/severe combined immunodeficient/interleukin (NOD/SCID/IL)2r gamma(null) mice carrying a complete null mutation of the cytokine gamma c upon the SCID background. Using this model, we demonstrated that LS cells exclusively recapitulate AML and retain self-renewal capacity in vivo. They home to and engraft within the osteoblast-rich area of the bone marrow, where AML cells are protected from chemotherapy-induced apoptosis. Quiescence of human LS cells may be a mechanism underlying resistance to cell cycle-dependent cytotoxic therapy. Global transcriptional profiling identified LS cell-specific transcripts that are stable through serial transplantation. These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells.

High levels of plasma HHV-6 DNA are associated with higher risk of HHV-6 encephalitis. UCBT is a significant risk factor for HHV-6 encephalitis. HHV-6 encephalitis should be considered if CNS dysfunction develops concomitant to high-level plasma HHV-6 DNA after allogeneic HCT.

a b s t r a c t a-Axis-oriented undoped n-BaSi 2 epitaxial films were grown on Si(111) substrates by molecular beam epitaxy, and the crystalline quality and grain boundaries were investigated by means of reflection highenergy electron diffraction, X-ray diffraction, and transmission electron microscopy (TEM). The grain size of the BaSi 2 films was estimated to be approximately 0.1-0.3 mm, and straight grain boundaries (GBs) were observed in the plan-view TEM images. Dark-field TEM images under a two-beam diffraction condition showed that these GBs consist mostly of BaSi 2 {011} planes. The diffusion length of minority carriers in nBaSi 2 was found to be approximately 10 mm by an electron-beam-induced current technique.

and 5 The Jackson Laboratory, Bar Harbor, Maine, USA The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34 þ CD38À fraction. To understand the origin of malignant cells in primary human B-precursor acute lymphocytic leukemia (B-ALL), we established a novel in vivo xenotransplantation model. Purified CD34 þ CD38 þ CD19 þ , CD34 þ CD38ÀCD19 þ and CD34 þ CD38ÀCD19À bone marrow (BM) or peripheral blood (PB) cells from three pediatric B-ALL patients were intravenously injected into sublethally irradiated newborn NOD/ SCID/IL2rc null mice. We found that both CD34 þ CD38 þ CD19 þ and CD34 þ CD38ÀCD19 þ cells initiate B-ALL in primary recipients, whereas the recipients of CD34 þ CD38ÀCD10À CD19À cells showed normal human hematopoietic repopulation. The extent of leukemic infiltration into the spleen, liver and kidney was similar between the recipients transplanted with CD34 þ CD38 þ CD19 þ cells and those transplanted with CD34 þ CD38ÀCD19 þ cells. In each of the three cases studied, transplantation of CD34 þ CD38 þ CD19 þ cells resulted in the development of B-ALL in secondary recipients, demonstrating self-renewal capacity. The identification of CD34 þ CD38 þ CD19 þ self-renewing B-ALL cells proposes a hierarchy of leukemia-initiating cells (LICs) distinct from that of AML. Recapitulation of patient B-ALL in NOD/SCID/IL2rc null recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.

Human herpes virus (HHV)6-associated limbic encephalitis and/or myelitis is one of the life-threatening central nervous system complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recent reports have shown significant correlations of these complications with unrelated cord blood transplantation (UCBT). We retrospectively analyzed 228 allogeneic HSCT recipients in our single institution; 13 patients (5.7%) were diagnosed with HHV6-associated encephalitis/myelitis. This complication was documented in 8 of 51 UCBT recipients (15.7%) and 5 of 177 recipients (2.8%) transplanted with bone marrow or peripheral blood stem cells, indicating a higher incidence of this complication occurring in UCBT recipients (P = .0005). In addition, HHV6-associated encephalitis/myelitis occurred more frequently in recipients who underwent 2 or more HSCTs (7 of 59 recipients [11.9%]), compared to those who received only 1 HSCT (6 of 169 recipients [3.6%], P = .018). Of note, the incidence of this complication increased to 28.6% (6 of 21 recipients), when the analysis was restricted to a second or more UCBT recipients. All 13 patients presented preengraftment immune response prior to the onset of encephalitis. Two patients manifested typical symptoms at the onset of HHV6-associated encephalitis/myelitis, such as memory dysfunction, disorientation, and consciousness disturbance. However, 4 patients presented only with dysesthesia and pruritus, described as typical manifestations of patients with calcineurin-inhibitor-induced pain syndrome (CIPS), and the remaining 7 showed both symptoms, indicating that CIPS-like symptoms might be manifestations of HHV6-associated myelitis. Thus, physicians should be alert to this rare but often fatal complication, particularly for those who receive 2 or more HSCTs using UCB.