Results: 4

1.
Figure 1

Figure 1. VEC-Cre-mediated Pten loss leads to MPD and leukaemogenesis. From: Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation.

a, Survival curve for mouse littermate pairs. Inset: representative spleens from mice at postnatal day 60 (P60). Mut, mutant; WT, wild type. b, Progressive alterations in PB: 30 littermate pairs (W, wild-type; M, mutant) per time point. Bars show the data range; points show averages. WBC, white blood cells. c, Identification of blast population by CD45/SSC plot in BM and spleen. The blasts were sorted for Giemsa–Wright staining, PCR genotyping and lineage analyses. Δex5, exon-5-deleted Pten allele.

Wei Guo, et al. Nature. ;453(7194):529-533.
2.
Figure 2

Figure 2. Self-renewing LSCs are enriched in the c-KitmidCD3+ compartment. From: Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation.

a, LSC identification. The experimental design is illustrated in Supplementary Fig. 3. Top: illustration of the three subpopulations that were sorted from BM of five independent leukaemic donor mice (cell fractions are denoted on each FACS plot). Bottom: summary of independent transplantation experiments with sorted and serially diluted cells. +, leukaemia development; −, leukaemia-free for more than 100 days; n.a., viable cells after sorting were not enough for transplantation. b, LSCs are self-renewing and lead to accelerated leukaemogenesis during serial transplantations. Top: illustration of the experimental procedure. Bottom: summary of the results. Red lines in the lower chart represent the means of leukaemia latencies.

Wei Guo, et al. Nature. ;453(7194):529-533.
3.
Figure 3

Figure 3. β-Catenin activation in LSCs and its role in leukaemogenesis. From: Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation.

a, Accumulation of unphosphorylated β-catenin in blasts. Cytospin slides with thymic cells were stained with the monoclonal antibody 8E4, which recognizes unphosphorylated β-catenin. Top: representative fluorescent images. CP, chronic phase; BC, blast crisis. Scale bars, 25 μm. Bottom: representative confocal images. DAPI, 4′,6-diamidino-2-phenylindole. Original magnification ×100. b, Marked increase in unphosphorylated β-catenin levels in the LSC and blast populations. BM cells were pooled from two blast-crisis or WT littermates and were lineage (Lin)-depleted before FACS analysis. c, Decreased and delayed leukaemogenesis after ablation of one allele of Ctnnb1. Kaplan–Meier survival curves with Logbank statistical analysis (denoted on the curves) summarize leukaemia development in transplantation experiments. Blue line, PtenloxP/loxP;Ctnnb1loxP/+;VEC-Cre+; green line, PtenloxP/loxP;VEC-Cre+.

Wei Guo, et al. Nature. ;453(7194):529-533.
4.
Figure 4

Figure 4. The recurring translocation T(14;15) involves the Tcra/Tcrd cluster and the c-myc gene and results in aberrant overexpression of c-myc in LSCs and T-ALL blasts. From: Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation.

a, Detection of T(14;15) by SKY analysis in metaphases prepared directly from BM of colcemid-treated WT or mutant mice. b, Breakpoint (BP) identification by two-colour FISH analysis. The results with green-labelled and red-labelled BAC probes are illustrated in the lower images and explained in the upper diagram. c, A schematic mapping of the T(14;15) translocation. BP, breakpoint. mChr, mouse chromosome. d, Recurring T(14;15) in primary T-ALL mutants and transplants with chronic-phase BM (BMT), splenic (SpT) or LSC cells was analysed by metaphase SKY (mSKY), metaphase FISH (mFISH) and interphase FISH (iFISH). Values shown are percentages. e, c-myc messenger RNA overexpression (means ± s.d.) in both primary blast-crisis (BC) mice and leukaemia transplants was detected by RT–PCR and analysed by Student's t-test. CP, chronic phase; Ct control, WT littermates (for primary mice) or an unrelated SCID mouse (for WT and leukaemic transplants). f, Overexpression of c-myc only in CD3+ splenic cells of T-ALL (n = 3). The percentage with c-myc overexpression in the CD3 or CD3+ compartment is denoted in parentheses. Grey, control (a mixture of WT and T-ALL cells); blue, WT; red, T-ALL.

Wei Guo, et al. Nature. ;453(7194):529-533.

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