Abstract P175: Investigating inositol polyphosphate-4-phosphatase, type II (INPP4B) signaling and role in acute myeloid leukemia
Bibliographic record
Abstract
Abstract Acute myeloid leukemia (AML) is an aggressive clonal stem cell disorder characterized by invasion of bone marrow, impaired hematopoiesis and accumulation of functionally immature myeloblasts. Our previous studies demonstrated that the expression level of the lipid phosphatase, INPP4B, is associated with poor outcomes in AML. To gain an understanding of the role of Inpp4b in AML progression, we performed RNA sequencing on Inpp4b+/+ and Inpp4b−/− MLL-AF9 leukemias. Analysis of RNA sequencing data revealed that a disproportionately large number of lysosomal gene transcripts are decreased in Inpp4b−/− leukemias; these include cathepsins and lysosomal specific proteases responsible for proteolysis. This discovery provided evidence supporting a potential role for INPP4B in the lysosomal pathway. To validate these findings, immunofluorescence staining of the lysosomal protein LAMP1 was performed, which revealed a greater number of lysosomes in U2OS cells overexpressing INPP4B, and a decrease in lysosome number upon siRNA knockdown of INPP4B. Subsequently the DQ-BSA staining was used to assess INPP4B’s effect on lysosomal function. In both U2OS and the leukemia cells, we observed that INPP4B expression is positively associated with the proteolytic activity of lysosomes. Currently we are testing the role of INPP4B expression on sensitivity to lysosomal inhibitors; Lys05, Chloroquine, and Mefloquine. Overall, we aim to uncover how INPP4B expression in AML controls lysosomal mechanisms and biology and to test putative therapeutic strategies to exploit this pathway. Citation Format: Keyue Chen, Gizem E. Genc, John F. Woolley, Daniel K.C. Lee, Roberto J. Botelho, Leonardo Salmena. Investigating inositol polyphosphate-4-phosphatase, type II (INPP4B) signaling and role in acute myeloid leukemia [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P175.
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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".