The Top secret Equipment For A-674563
Clonal Stability after Serial Transplantation Next, we tested whether leukemias were transplantable and whether the leukemic subtypes, as assessed by organ involvement, A-674563 tissue morphology, and immune phenotype, were maintained from the original donor to the recipients. For this purpose, we serially transplanted bone marrow cells from leukemic mice into secondary recipients. Once more, it appeared that leukemias behaved unpredictably when challenged by serial transplantation. For that matter, we describe these serial transplantation studies case by case. Heritability of Clonal Dominance and Leukemia Phenotype In the first serial transplantation experiment (Figure?4A), we observed a very stable pattern of both disease phenotype and clonal dominance. Three secondary recipient mice transplanted with bone marrow cells from a primary recipient with a monoclonal T?cell leukemia all developed T?cell leukemias as well (Figures 4B and 4C; also see Table S1). Barcode analyses revealed that the disease-causing clone was identical in the donor mouse and all individual recipients (Figure?4D, mouse 1 donor, and recipients 1-1, 1-2, 1-3, clone 1). Figure?4 Heritability of Clonal Dominance and Disease Phenotype Clonal Instability after Serial Transplantation Although the behavior of some clones remained unaltered, we frequently observed the appearance of different IKK inhibitor leukemic phenotypes after serial transplantation (Figures 5, ?,6,6, Digoxin S4, S5A, and S7). Immature (Figures 5A�C5C) and erythroid leukemias (Figures 6A�C6C and S7A�CS7C) appeared after serial transplantation of bone marrow cells from T?cell leukemic mice. In these cases, malignant cells from the recipient mouse displayed different cell-surface markers [for example, lineage negative (Figures 5A and 5C, mouse 4-3) or TER119+ (Figures 6A and 6C, mouse 5-5; Figures S7A and S7C, mouse 2-3)] instead of CD3��+, which was expressed on the leukemic cells from the donor (also see Table S1). In both these cases, lymph nodes were not enlarged, while this is typical for T?cell leukemias (Figure?S4). Figure?5 Activation of a Dormant LCS Clone Result in the Appearance of an Undifferentiated Leukemia Subtype Figure?6 Activation of LCS Clones after Serial Transplantation To test whether these secondary leukemias were correctly identified as a different subtype, we assessed genome-wide gene expression from spleen cells from six T?cell leukemic mice, five erythroid mice, and one mouse that developed an immature leukemia (Figures 5E, ?E,6E,6E, ?E,7E,7E, and S5B). Figure?7 Differentiation of Immature LSC Clones Three hundred forty-three genes showed significantly higher expression in T?cell leukemias compared with erythroid leukemias, while conversely, 225 genes were significantly upregulated in erythroid leukemias as compared with T?cell leukemias (Benjamini Hochberg, p?
