Expression of CD99 in T-ALL and normal hemopoietic cells.

<p>(A) Expression of CD99 antigen was assessed by flow cytometry in BM samples from 9 T-ALL cases and BM MNC, CD34⁺/CD38^- HSC and CD3⁺ T cells from 5–9 healthy donors. Lines represent median values, ** <i>P</i>≤0.007, **** <i>P</i><0.0001. (B) Expression of CD99 in sorted LPC subpopulations from this T-ALL cohort. Lines represent median values, * <i>P</i> = 0.02, ** <i>P</i>≤0.009. (C) Stacked bar chart showing expression of CD99 in CD34/CD7 LPC subpopulations in individual cases. (D) Gene expression in BM samples from 5 T-ALL cases (pts 2, 4, 7, 8, 9) and from 5 healthy donors were analyzed using Agilent Whole Genome Oligo microarrays. Data shows side by side comparisons of median centered normalized log2 signal intensities. Boxes represent the range of expression and the horizontal lines represent the median.</p

Frequency of LPC in CD34/CD99 subpopulations.

<p>Frequency of LPC in CD34/CD99 subpopulations.</p

Patient sample characteristics.

<p>Patient sample characteristics.</p

Crosstalk between ß-catenin and WT1 signalling activity in acute myeloid leukemia

No description supplie

LEF-1 drives aberrant ß-catenin nuclear localization in myeloid leukemia cells

Canonical Wnt/ß-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized ß-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia patients; however, some patients exhibit little or no nuclear ß-catenin even where cytosolic ß-catenin is abundant. Control of the subcellular localization of ß-catenin therefore represents an additional mechanism regulating Wnt signaling in hematopoietic cells. To investigate the factors mediating the nuclear-localization of ß-catenin we carried out the first nuclear/cytoplasmic proteomic analysis of the ß-catenin interactome in myeloid leukemia cells and identified putative novel ß-catenin interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear ß-catenin) versus Wnt-unresponsive cells (low nuclear ß-catenin) suggested the transcriptional partner, LEF-1, could direct the nuclear-localization of ß-catenin. The relative levels of nuclear LEF-1 and ß-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF-1 knockdown perturbed ß-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF-1 overexpression was able to promote both nuclear-localization and ß-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This is the first ß-catenin interactome study in hematopoietic cells and reveals LEF-1 as a mediator of nuclear ß-catenin level human myeloid leukemia