Hox regulation of normal and leukemic hematopoietic stem cells
Bibliographic record
Abstract
PURPOSE OF REVIEW: Herein we focus on recent studies of knock out mice that demonstrate a function for the clustered homeobox (Hox) genes in normal hematopoiesis, on papers that point to their general involvement in human leukemia, and discuss the advances in the understanding of the mechanisms underlying their role in these processes. RECENT FINDINGS: Expression analysis and gain- or loss- of function studies have shown that Hox play an important role in the regulation of early stages of hematopoiesis, including the self-renewal of hematopoietic stem cells (HSCs)/early progenitors. In the area of leukemia, numerous models of murine leukemia have demonstrated a role for Hox in the pathobiology of the disease. Moreover, the identification of multiple Hox genes as partners of chromosomal translocations and the observed global deregulation of Hox genes and cofactors demonstrated by gene profiling of cells from leukemic patients, have unequivocally shown a major function for Hox genes and cofactors in a wide spectrum of human leukemia. SUMMARY: The identification of Hox genes as HSC regulators has been exploited to develop strategies to efficiently expand HSCs ex vivo, a key step to the success of therapies based on HSC transplantation and the understanding of mechanisms underlying HSC regulation. As leukemia is the result of deregulation of normal HSC development, the elucidation of the role of Hox in the pathobiology of the disease is helping to understand how HSCs self-renew and differentiate, and moreover, should facilitate the development of strategies for the management of leukemia.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".