Prognostic Value of the Expression of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR-1) in Chronic Lymphocytic Leukemia
Abstract
Background: The transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1) has acted on the causation and sustentation of mature B cell lymphomagenesis for chronic lymphocytic leukemia (CLL) cells. The aim of this study was to show whether there is a relationship between the level of ROR1 surface expression in CLL cells and disease findings.
Materials and Methods: The level of ROR1 cell surface expression was determined in accordance with the flow cytometric analysis of CLL patients at the first diagnosis time. 2 groups were formed according to the high and low ROR1 levels. The cut-off point to the ROR1 level was calculated for advanced-stage disease by using receiver operating characteristic (ROC) curves. A two-sided p-value <0,05 was considered statistically significant.
Results: 108 CLL cases with a median age of 60 were enrolled. The median percentage of ROR1 cell surface marker positivity in the CD5/CD19 positive leukemic cell was 62%. The CLL cases with high ROR1 levels have thrombocytopenia (p=0.042), anemia (p=0.028), and high beta 2 microglobulin value ≥3 mg/dL (p=0.002) and the need for first-line treatment (p=0.043).
Conclusion: The poor prognostic parameters such as splenomegaly, anemia, higher beta 2 microglobulin levels, intermediate/advanced RAİ stage disease, and need for first-line treatment had associated high-level ROR 1 expression of our CLL patients. It needs to be investigated for its effect on predicting disease burden and aggressiveness with more comprehensive studies on ROR1 expression levels in CLL cases.
2. Zhang S, Chen L, Wang-Rodriguez J, et al. The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. Am J Pathol. 2012;181(6):1903-10.
3. Yu J, Chen L, Cui B, et al. Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation. J Clin Invest. 2016; 126(2):585-598.
4. Hojjat-Farsangi M, Moshfegh A, Daneshmanesh AH, et al. The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer therapy. Semin Cancer Biol. 2014;29:21-31.
5. Baskar S, Kwong KY, Hofer T, et al. Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clin Cancer Res. 2008;14(2):396-404.
6. Cui B, Ghia EM, Chen L, et al. High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia. Blood. 2016;128(25):2931–2940.
7. Mani R, Mao Y, Frissora FW, et al. Tumor antigen ROR1 targeted drug delivery mediated selective leukemic but not normal B-cell cytotoxicity in chronic lymphocytic leukemia. Leukemia. 2015;29(2):346-55.
8. Daneshmanesh AH, Hojjat-Farsangi M, Khan AS, et al. Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells. Leukemia. 2012;26(6):1348-55.
9. Widhopf GF II, Cui B, Ghia EM, et al. ROR1 can interact with TCL1 and enhance leukemogenesis in Eμ-TCL1 transgenic mice. Proc Natl Acad Sci USA. 2014;111(2):793-798.
10. Daneshmanesh AH, Mikaelsson E, Jeddi-Tehrani M, et al. Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy. Int J Cancer. 2008;123(5):1190-5.
11. Janovska P, Poppova L, Plevova K, et al. Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2016;22(2):459–469.
12. Broome HE, Rassenti LZ, Wang HY, et al. ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia. Leuk Res. 2011;35(10):1390–1394.
13. Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123(21):3247-54.
14. Fayad L, Keating MJ, Reuben JM, et al. Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood. 2001;97(1):256-63
15. Moreno A, Villar ML, Cámara C, et al. Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells. Blood. 2001;97(1):242-9.
16. Li P, Harris D, Liu Z, et al. Stat3 activates the receptor tyrosine kinase like orphan receptor-1 gene in chronic lymphocytic leukemia cells. PLoS One. 2010;5(7):e11859.
17. Pflug N, Bahlo J, Shanafelt TD, et al. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014;124(1):49-62.
Files | ||
Issue | Vol 17, No 1 (2023) | |
Section | Original Article(s) | |
DOI | https://doi.org/10.18502/ijhoscr.v17i1.11712 | |
Keywords | ||
The transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1); Chronic lymphocytic leukemia (CLL) |
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