Abstract 3335: The high cMyc expression characterizes a small cell subpopulation in ALK-positive anaplastic large cell lymphoma that carry cancer stem-like properties
Bibliographic record
Abstract
Abstract We have previously identified two phenotypically distinct cell subpopulations in ALK+ anaplastic large cell lymphoma (ALK+ALCL) based on their differential response to a Sox2 reporter (SRR2), with reporter responsive (RR) cells being more tumorigenic and chemoresistant than reporter unresponsive (RU) cells. The regulation of the RU/RR dichotomy remains to be elusive. Our bioinformatics analysis of the SRR2 sequence suggests that cMyc may be an important factor. In support of this concept, we found a substantially higher expression of cMyc and more cMyc and Sox2-SRR2 probe bindings in RR cells than in RU cells. Inhibition of cMyc in RR cells significantly decreased SRR2 luciferase activity, and overexpression of cMyc in RU cells significantly increased SRR2 luciferase activity. Correlating with this, cMyc inhibition in RR cells significantly attenuated the clonogenicity and sensitized cells to doxorubicin; while overexpression of cMyc in RU cells conferred to the potentiated clonogenicity and chemoresistance. Importantly, we found cMyc not only maintains Sox2 protein expression, but also promotes Sox2 SRR2 probe binding and its transcriptional activity. Moreover, we found the highly active Wnt canonical pathway (WCP) contributes to the high expression of cMyc in RR cells. Intriguingly, we observed a positive regulatory loop in RR cells, in which Sox2 up-regulates Wnt2B, which can activate the WCP and cMyc. Furthermore, the significance of cMyc in this context was further highlighted by the fact that RU cells with stably transfected c-MYC are phenotypically similar with RR cells in terms of the elevated activation of WCP and increased tumorigenicity in vivo. Lastly, we found cMyc is heterogeneously expressed in ALK+ALCL tumor cells (n = 5) by immunohistochemcial staining, and it co-localizes with active β-catenin, a marker of active WCP, in tumor cells by immunofluorescence assay. In conclusion, cMyc is a key regulatory factor in the determination of RU/RR dichotomy, which is linked to tumorigenic potential and chemo-resistance in ALK+ALCL. Citation Format: Chengsheng Wu, Haifeng Zhang, Nidhi Gupta, Alshareef Abdulraheem, Qian Wang, Yunghsin Huang, Raymond Lai. The high cMyc expression characterizes a small cell subpopulation in ALK-positive anaplastic large cell lymphoma that carry cancer stem-like properties. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3335.
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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) | 0.003 | 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".