Prognostic Importance of DUSP22 (Dual Specificity Phosphatase 22) Gene Expression in Low-Grade Lymphomas
Objectives: Dual specificity phosphatase 22 (DUSP22) is a novel phosphatase and has been demonstrated to be a cancer suppressor gene associated with various biological and pathological processes. The aim of this study is to evaluate the prognostic importance of DUSP22 expression in low-grade lymphomas.
Methods: Fluorescence in situ hybridization (FISH) was used to detect DUSP22 and 76 cases with indolent lymphoma were evaluated for DUSP22 expression. Thirty-nine had follicular lymphoma (FL), 30 had marginal zone lymphoma (MZL) and 7 had chronic lymphocytic leukemia (CLL).
Results: DUSP22 expression was detected in 17 cases (22.3%). The mean overall survival (OS) was found to be longer in cases without DUSP22 compared to cases with DUSP22 expression while event-free survival (EFS) was not different between the cases according to the DUSP22 expression. In univariate analysis, stage (early-stage disease p=0.0001), gender (female p=0.009) and DUSP22 expression (p=0.018) were found to be independent prognostic factors according to Cox regression analysis. .
Conclusion: There is no sufficient data about the clinical and/or prognostic significance of DUSP22 rearrangement in lymphomas except ALK (-) anaplastic large cell lymphoma. We found that DUSP22 is poor prognostic indicator in cases with low grade lymphomas.
1.Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 2014;124:1473–80.
2. Kao EY, Mukkamalla SKR, Lynch DT. ALK Negative Anaplastic Large Cell Lymphoma. Treasure Island (FL): StatPearls Publishing; 2021.
3. Pedersen MB, Hamilton-Dutoit SJ, Bendix K, Ketterling RP, Bedroske PP, Luoma IM, et al. DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study. Blood 2017;130:554–7.
4. Shen Y, Luche R, Wei B, Gordon ML, Diltz CD, Tonks NK. Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JSP-1. Proc Natl Acad Sci U S A 2001;98:13613–8.
5. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001;81:807–69.
6. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001;410:37–40.
7. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001;22:153–83.
8. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000;103:239–52.
9. Alonso A, Merlo JJ, Na S, Kholod N, Jaroszewski L, Kharitonenkov A, et al. Inhibition of T cell antigen receptor signaling by VHR-related MKPX (VHX), a new dual specificity phosphatase related to VH1 related (VHR). J Biol Chem 2002;277:5524–8.
10. Chen AJ, Zhou G, Juan T, Colicos SM, Cannon JP, Cabriera-Hansen M, et al. The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. J Biol Chem 2002;277:36592–601.
11. Li JP, Yang CY, Chuang HC, Lan JL, Chen DY, Chen YM, et al. The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck. Nat Commun 2014;5:3618.
12. Jeffrey KL, Camps M, Rommel C, Mackay CR. Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 2007;6:391– 403.
13. Chevret E, Prochazkova M, Beylot-Barry M, Merlio JP. A suggested protocol for obtaining high-quality skin metaphases from primary cutaneous T-cell lymphoma. Cancer Genet Cytogenet 2006;167:89–91.
14. Feldman AL, Law M, Remstein ED, Macon WR, Erickson LA, Grogg KL, et al. Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 2009;23:574–80.
15. Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, Vergier B, Jouary T, Beylot-Barry M, et al. IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases. J Invest Dermatol 2010;130:816–25.
16. Feldman AL, Dogan A, Smith DI, Law ME, Ansell SM, Johnson SH, et al. Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood 2011;117:915– 9.
17. Karai LJ, Kadin ME, Hsi ED, Sluzevich JC, Ketterling RP, Knudson RA, et al. Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am J Surg Pathol 2013;37:1173–81.
18. Onaindia A, de Villambrosía SG, Prieto-Torres L, Rodríguez-Pinilla SM, Montes-Moreno S, González-Vela C, et al. DUSP22-rearranged anaplastic lymphomas are characterized by specific morphological features and a lack of cytotoxic and JAK/STAT surrogate markers. Haematologica 2019;104:158–62.
19. Yu D, Li Z, Gan M, Zhang H, Yin X, Tang S, Wet al. Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients. Tumour Biol 2015;36:8531–5.