We demonstrate here that GSK-3 maintains the MLLleukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation.
The H3K4-specific demethylase KDM5B negatively regulates leukemogenesis in murine and human MLL-rearranged AML cells, demonstrating a crucial role for the H3K4 global methylome in determining LSC fate.
ChIP-Seq/qPCR analysis in MLL-r mouse models revealed aberrant epigenetic modifications with increased H3K79me2, and decreased H3K9me3 and H3K27me3 levels in LSCs, which may account for the high expression levels of Pbx3.
Actually, in patients, SCL transcription initiated at promoter 1b is restricted to primitive CD34+CD41- progenitor cells, while it is detectable in both cell subsets from healthy subjects; (iii) the full-length isoform of SCL protein is present in patients' CD34+ cells and in PBMC; in the latter the SCL-expressing cells mainly belong to the MK lineage in which its sublocalization is both nuclear and cytoplasmic, which contrasts with the sole nuclear staining observed in normal MK cells.
The interstitial deletion at 1p32 involving SIL (SCL-interrupting locus)/SCL (stem cell leukemia) is a case involving two non-V(D)J sites that have been suggested to be V(D)J recombination mistakes.
The SCL gene, initially discovered at the site of a translocation breakpoint associated with the development of a stem cell leukemia, encodes a protein that contains the highly conserved basic helix-loop-helix (bHLH) motif found in a large array of eukaryotic transcription factors.
This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis.
We previously showed that mouse fetal liver (FL) hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell Leukaemia (SCL) gene enhancer transgene (SCL-PLAP<sup>+</sup> cells), had robust endothelial engraftment potential when transferred to the blood stream of newborns or adult conditioned recipients, compared to the scarce vascular contribution of adult bone marrow cells.
We have identified the human gene, SCL.We discovered this gene because of its involvement in a chromosomal translocation associated with the occurrence of a stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities.
In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-).
The interstitial deletion at 1p32 involving SIL (SCL-interrupting locus)/SCL (stem cell leukemia) is a case involving two non-V(D)J sites that have been suggested to be V(D)J recombination mistakes.
SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis.
This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
The SCL gene, initially discovered at the site of a translocation breakpoint associated with the development of a stem cell leukemia, encodes a protein that contains the highly conserved basic helix-loop-helix (bHLH) motif found in a large array of eukaryotic transcription factors.
SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis.
The SCL gene, initially discovered at the site of a translocation breakpoint associated with the development of a stem cell leukemia, encodes a protein that contains the highly conserved basic helix-loop-helix (bHLH) motif found in a large array of eukaryotic transcription factors.