Abstract 464: CXCR7 protein is strongly expressed in B-acute lymphoblastic leukemia (ALL) but not in T-ALL or acute myelogenous leukemia
Bibliographic record
Abstract
Abstract The identification of CXCR7 in addition to CXCR4 as a receptor for the chemokine CXCL12/SDF-1 and recent reports that CXCR7 is expressed in many cancers including breast, lung and prostate prompted us to evaluate the role of CXCR7 in hematological malignancies. While CXCR4 is known to be involved in the progression of acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML), the role of CXCR7 in leukemic dissemination remains unknown. Using immunohistochemistry, we evaluated the expression patterns of CXCR7 and CXCR4 in tissue microarrays (TMAs) constructed from bone marrow biopsies obtained from patients diagnosed with pre B- and B-ALL (n=75; median age 5 yrs, range 6 mo-72 yrs), T-ALL (n=11; median age 12 yrs, range 4-29 yrs) and AML (n=140; median age 62 yrs, range 1-83 yrs). CXCR7 expression was also evaluated at the gene and protein levels in peripheral blood mononuclear cells from ALL and AML patients and in B-cell lines (Raji, NC-37, Ramos, Nalm-6, Reh), T-cell lines (Jurkat, Hut-102B, Sez-4, CEM), and myeloid cell lines (KG-1, HL-60, THP-1, U-937, K562, HEL) using RT-PCR and flow cytometry. We found that in B-and preB-ALL TMAs, CXCR7 was immunopositive in 79% of the patients, in contrast to negative immunostaining in 100% of T-ALL and AML samples. Consistently, flow cytometry showed that CXCR7 protein is expressed on the surface of preB-ALL cells, but not on T-ALL, AML or normal controls. CXCR7 surface expression in the cell lines studied showed that three (NC-37, Raji, Reh) out of five B-cell lines expressed CXCR7, but not in any of the T-cell lines, and only weakly in one (KG-1) of six myeloid cell lines studied. Analysis of the functional role of CXCR7 in leukemia revealed that CXCR7 did not mediate chemotaxis of CXCR7-positive NC-37 B-cell line and CXCR7-negative HL-60 myeloid cell line towards an SDF-1 gradient. However, CXCR7 was found to mediate the trans-endothelial migration, adhesion to HUVEC and survival of NC-37 cells, but not the adhesion to HUVEC or survival of HL-60 cells. In conclusion, the selective strong expression of CXCR7 in B-ALL but not in T-ALL or AML suggests a differential role this protein may play in various types of leukemia. As CXCR7 mediates trans-endothelial migration, adhesion and survival of B-cell line, further investigations into the functional role of CXCR7 in primary B-ALL are warranted with the aim of identifying new therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 464. doi:1538-7445.AM2012-464
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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".