A5099075506- RNA Research and Splicing
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Acute Myeloid Leukemia Research
University of Washington
2024-2025
Abstract Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences human HSCs progenitors (HSPCs) remain unclear. Here, we identify program HSPCs as a targetable vulnerability precise gene editing K700E primary CD34+ cells. Mutant induced pervasive reduced expression genes regulating mitosis genome maintenance leading to altered...
Myelodysplastic syndromes (MDS) are clonal stem cell disorders driven by heterogeneous genetic alterations leading to variable clinical course. MDS with splicing factor SF3B1 mutations is a distinct subtype favorable outcome. However, selected co-mutations induce poor prognosis and how these lesions cooperate in human hematopoietic progenitor cells (HSPCs) during disease progression still unclear. Here, we integrated molecular profiling of patients gene editing primary iPSC-derived HSPCs...
<p>Supplemental Table 3. Drug screening of WT (Ctrl), SF3B1 K700E (S-A), SF3B1/RUNX1 (S-R), and SF3B1/STAG2 (S-S) K562 cells with the AML OncoPanel1 165 FDA-approved compounds.</p>
<p>Supplemental Table 2. Splicing analysis of WT and SF3B1 K700E mutant K562 cells.</p>
<p>Supplemental Table 2. Splicing analysis of WT and SF3B1 K700E mutant K562 cells.</p>
<p>Supplementary Figure S1: Multiplex gene editing of SF3B1 K700E in CD34+ cells. Supplementary S2: Splicing and single cell transcriptome analysis SF3B1-mutant HSPCs. S3: Mis-splicing expression BUBR1 CDC27. S4: Drug sensitivity S5: The role candidate mis-spliced genes CHK1i sensitivity. S6: Prexasertib testing CB HSPCs, MDS samples, vivo.</p>
<p>Supplemental Table 1. Splicing analysis of control and SF3B1 K700E edited cord blood (CB) peripheral (PB) CD34+ cells.</p>
<p>Supplemental Table 3. Drug screening of WT (Ctrl), SF3B1 K700E (S-A), SF3B1/RUNX1 (S-R), and SF3B1/STAG2 (S-S) K562 cells with the AML OncoPanel1 165 FDA-approved compounds.</p>
<p>Supplementary Figure S1: Multiplex gene editing of SF3B1 K700E in CD34+ cells. Supplementary S2: Splicing and single cell transcriptome analysis SF3B1-mutant HSPCs. S3: Mis-splicing expression BUBR1 CDC27. S4: Drug sensitivity S5: The role candidate mis-spliced genes CHK1i sensitivity. S6: Prexasertib testing CB HSPCs, MDS samples, vivo.</p>
<p>Supplemental Table 1. Splicing analysis of control and SF3B1 K700E edited cord blood (CB) peripheral (PB) CD34+ cells.</p>
<div>Abstract<p>Splicing factor <i>SF3B1</i> mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences human HSCs progenitors (HSPCs) remain unclear. Here, we identify program HSPCs as a targetable vulnerability precise gene editing K700E primary CD34<sup>+</sup> cells. Mutant SF3B1 induced pervasive reduced...
<div>Abstract<p>Splicing factor <i>SF3B1</i> mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences human HSCs progenitors (HSPCs) remain unclear. Here, we identify program HSPCs as a targetable vulnerability precise gene editing K700E primary CD34<sup>+</sup> cells. Mutant SF3B1 induced pervasive reduced...