Abstract 2292: Enforced expression of miR-125b promotes the in vivo expansion of human Lin- CB multi-lymphoid progenitors (MLP) and AML leukemia stem cells.
Bibliographic record
Abstract
Abstract We recently demonstrated stem cell gene signatures predict clinical outcome in acute myeloid leukemia (AML) (Eppert et. al., Nature Medicine, 2011). Concomitant to this work, miRNA signatures for hematopoietic stem cells (HSC) and leukemia stem cells (LSC) were also generated. miRNA are small non-coding RNAs that regulate the translation and mRNA stability of protein coding genes with significant roles in the maintenance of human HSC (Lechman et. al., Cell Stem Cell, in press). To understand the functional role of miRNA in normal human blood development, we undertook an in vivo over-expression screen of 10 miRNA candidates over-represented in HSC and LSC. Lineage depleted human umbilical cord blood cells (Lin- CB) were transduced with lentivirus expressing either a candidate miRNA or control vector and xeno-transplanted into NSG mice. Three miRNA displayed a competitive growth advantage while 4 miRNA induced a growth disadvantage along with skewing of lineage output. A top LSC array candidate, miR-125b, showed the most pronounced phenotype with overt expansion of marked cells, enlarged spleens and increased lymphoid and erythroid output. Detailed analysis of miR-125b grafts revealed a greatly expanded MLP population, in comparison to HSC and MPP. Furthermore, upon enforced in vivo expression of miR-125b in 3 AML patient samples, we observed large increases in the CD34+CD117+ populations for all three AML samples, suggesting increased LSC numbers. Secondary LDA experiments revealed up to a 34 fold increase in LSC activity in comparison to control vector transduced AML cells. These data suggest that miR-125b normally functions in the limited self-renewal of lymphoid committed early progenitors and this function may be usurped during leukemogenesis to enhance LSC self-renewal. Citation Format: Eric R. Lechman, Karin G. Hermans, Stephanie Dobson, Kolja Eppert, Mark Minden, John E. Dick. Enforced expression of miR-125b promotes the in vivo expansion of human Lin- CB multi-lymphoid progenitors (MLP) and AML leukemia stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2292. doi:10.1158/1538-7445.AM2013-2292
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".