Clonotypic myeloma cells able to xenograft myeloma to nonobese diabetic severe combined immunodeficient mice copurify with CD34 (+) hematopoietic progenitors.
Bibliographic record
Abstract
The identity of the multiple myeloma (MM) precursor(s) is unknown. Our objective was to determine the myelomagenic capabilities of CD34-enriched autografts. Hematopoietic progenitor fractions from fresh or cryopreserved granulocyte-colony-stimulating factor mobilized blood from myeloma patients were obtained by sorting or enrichment, followed by RT-PCR analysis of clonotypic transcripts and/or their ability to transfer myeloma to immunodeficient mice. CD34(+) enrichment using immunomagnetic methods comparable with those used clinically results in copurification of MM cells able to xenograft nonobese diabetic severe combined immunodeficient mice. Highly purified CD34(+) progenitors from granulocyte-colony-stimulating factor mobilized blood of myeloma patients include, on average, 31% clonotypic MM cells. CD34(+) progenitors also include 31% DNA aneuploid cells. For six of six MM patients, enriched progenitors were myelomagenic as measured by engraftment of clonotypic cells and/or the development of lytic bone lesions. Intrasternal injection of enriched progenitor fractions led to clonotypic cells in the femoral bone marrow and bone lesions at distant skeletal locations, confirming dissemination of myelomagenic cells. MM precursors copurify with normal hematopoietic progenitors, emphasizing the need for tumor-free grafts. Autologous MM engraftment is likely to be considerably more efficient than in a xenogeneic host, strongly suggesting that MM autografts contribute to posttransplant relapse. The xenografting myelomagenic component(s) is unlikely to be plasma cells, given the lack of morphologically identified plasma cells among enriched progenitors. Xenografting MM precursors appear to be CD34(+)CD45(low), similar to normal progenitors. Precursor function within the MM clone seems to be complex and may involve multiple components of the MM hierarchy.
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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 | 0.001 |
| 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".