Expression of nuclear pore protein POM121 in childhood acute lymphoblastic leukemias and its relationship with prognosis
Abstract
Purpose: We aimed to investigate the status of POM121 gene expression, which is one of the nuclear pore proteins in childhood acute lymphoblastic leukemias (ALL), compared with the normal population, and its relationship with prognosis and other clinical findings.
Materials and Methods: Fifty-nine patients with ALL followed up and treated between January 2008 and November 2013, and 36 control subjects were included in the study. A real-time PCR method was used to detect POM121 gene expressions.
Results: The mean value of POM121 expression was 3.75±2.91 in ALL patients and 3.32±3.76 in the control group. The 3 and 10 year overall survival (OS) was better in ALL with lower POM121 expression (77%, 70% versus 68%, 58%, respectively). Although the OS was better in B-ALL patients, with lower POM121 expression (84%, 75% versus 54%, 46%, respectively), in T-ALL, in contrast, the OS results were better in patients with a higher POM121 expression (90%, 90% versus 60%, 60%, respectively). Patients with a higher POM121 expression than the mean of the control group and who had relapse and central nervous system involvement had statistically significantly lower OS results in the 3rd and 10th years (16%, 0% versus 84%, 78%, respectively).
Conclusion: High POM121 expression negatively affects the prognosis in patients with ALL. This is a study to show the relationship between POM121 expression and prognosis in childhood acute lymphoblastic leukemias, POM121 function will be clarified further with more comprehensive studies.
Supporting Institution
Cukurova University Research Projects Funding Unit
Project Number
TF2013 LTP30
Thanks
This work was supported by ‘Cukurova University Research Projects Funding Unit’ with Project number TF2013 LTP30.
References
- Jühlen R, Fahrenkrog B. Moonlighting nuclear pore proteins: tissue-specific nucleoporin function in health and disease. Histochem Cell Biol. 2018;150:593-605.
- Nofrini V, Giacomo DD, Mecucci C. Nucleoporin genes in human diseases. Eur J Hum Genet. 2016;24:1388-95.
- Xu S, Powers MA. Nuclear pore proteins and cancer. Semin Cell Dev Biol. 2009; 20:620–30.
- Schwartz TU. The structure inventory of the nuclear pore complex. J Mol Biol. 2016;428:1986-2000.
- Roy A, Narayan G. Oncogenic potential of nucleoporins in non-hematological cancers: recent update beyond chromosome translocation and gene fusion. J Cancer Res Clin Oncol. 2019;145:2901-10.
- Kindermann B, Valkova C, Krämer A, Perner B, Engelmann C, Behrendt L et al. The nuclear pore proteins Nup88/214 and T-cell acute lymphatic leukemia-associated NUP214 fusion proteins regulate Notch signaling. J Biol Chem. 2019;294:11741-50.
- Mendes A, Fahrenkrog B. NUP214 in leukemia: It's more than transport. Cells. 2019;8:76.
- Scandura JM, Boccuni P, Cammenga J, Nimer SD. Transcription factor fusions in acute leukemia: variations on a theme. Oncogene. 2002;21:3422-44.
- Takeda A, Yaseen NR. Nucleoporins and nucleocytoplasmic transport in hematologic malignancies. Semin Cancer Biol. 2014;27:3-10.
- Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas OA et al. Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia. 2009;23:134–43.
- Bousquet M, Broccardo C, Quelen C, Meggetto F, Kuhlein E, Delsol G et al. A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5. Blood. 2007;109:3417-23.
- Fortschegger K, Anderl S, Denk D, Strehl S. Functional heterogeneity of PAX5 chimeras reveals insight for leukemia development. Mol Cancer Res. 2014;12:595-606.
- Bain BJ, Barnett D, Linch D, Matutes E, Reilly JT. Revised guideline on immunophenotyping in acute leukaemias and chronic lymphoproliferative disorders. Clin Lab Haematol. 2002;24:1–13.
- Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer R, Möricke A et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115:3206-14.
- Kohler A, Hurt E. Gene regulation by nucleoporins and links to cancer. Mol Cell. 2010;38:6–15.
- Chow KH, Factor RE, Ullman KS. The nuclear envelope environment and its cancer connections. Nat Rev Cancer. 2012;12:196–209.
- Kraemer D, Wozniak RW, Blobel G, Radu A. The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm. Proc Natl Acad Sci USA. 1994;91:1519-23.
- Simon DN, Rout MP. Cancer and the nuclear pore complex. Adv Exp Med Biol. 2014;773:285-307.
- Wong RW. New activities of the nuclear pore complexes. Cells. 2021;10:2123.
- Denk D, Bradtke J, König M, Strehl S. PAX5 fusion genes in t(7;9)(q11.2;p13) leukemia: a case report and review of the literatüre. Mol Cytogenet. 2014;7:13.
- Rampello AJ, Laudermilch E, Vishnoi N, Prophet SM, Shao L, Zhao C et al. Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2. J Cell Biol. 2020;219:e201910185.
Çocukluk çağı akut lenfoblastik lösemilerinde nükleer por proteini POM121’in ekspresyonu ve prognoz ile ilişkisi
Abstract
Amaç: Bu çalışmada, çocukluk çağı akut lenfoblastik lösemilerinde (ALL), nükleer por proteinlerinden biri olan POM121’in gen ekspresyonunun normal popülasyona göre durumunu, prognoz ve diğer klinik bulgularla ilişkisini araştırmayı amaçladık.
Gereç ve Yöntem: Ocak 2008 ile Kasım 2013 tarihleri arasında takip ve tedavi edilen 59 ALL'li hasta ve 36 kontrol olgu çalışmaya dahil edildi. POM121 gen ekspresyonunu saptamak için Real time-PCR yöntemi kullanıldı.
Bulgular: POM121 ekspresyonunun ortalama değeri ALL hastalarında 3,75 ± 2,91 ve kontrol grubunda 3,32 ± 3,76 idi. 3 ve 10 yıllık sağkalım düşük POM121 ekspresyonuna sahip olan ALL hastalarında daha iyi idi (sırasıyla %77, %70’e karşı %68, %58). B-ALL hastalarında POM121 ekspresyonu, daha düşük olan hastaların GS sonuçları daha iyi iken (sırasıyla %84, %75’e karşı %54, %46) T-ALL'de, tersine, yüksek olan hastaların GS sonuçları, daha iyi idi (sırasıyla %90, %90’a karşı %60, %60). Nüks ve merkezi sinir sistemi tutulumu olan, kontrol grubunun ortalamasından daha yüksek POM121 ekspresyonu olan hastalar 3. ve 10. yıllarda istatistiksel olarak anlamlı şekilde daha düşük GS sonuçlarına sahipti (sırasıyla %16, %0’a karşı %84, %78).
Sonuç: Yüksek POM121 ekspresyonu, ALL hastalarında prognozu olumsuz yönde etkiler. Bu çalışma, çocukluk çağı akut lenfoblastik lösemilerinde POM121 ekspresyonu ile prognoz arasındaki ilişkiyi göstermeye yönelik yapılan bir çalışmadır ve POM121’in fonksiyonlarını açığa kavuşturmak için daha kapsamlı çalışmalar gereklidir.
Project Number
TF2013 LTP30
References
- Jühlen R, Fahrenkrog B. Moonlighting nuclear pore proteins: tissue-specific nucleoporin function in health and disease. Histochem Cell Biol. 2018;150:593-605.
- Nofrini V, Giacomo DD, Mecucci C. Nucleoporin genes in human diseases. Eur J Hum Genet. 2016;24:1388-95.
- Xu S, Powers MA. Nuclear pore proteins and cancer. Semin Cell Dev Biol. 2009; 20:620–30.
- Schwartz TU. The structure inventory of the nuclear pore complex. J Mol Biol. 2016;428:1986-2000.
- Roy A, Narayan G. Oncogenic potential of nucleoporins in non-hematological cancers: recent update beyond chromosome translocation and gene fusion. J Cancer Res Clin Oncol. 2019;145:2901-10.
- Kindermann B, Valkova C, Krämer A, Perner B, Engelmann C, Behrendt L et al. The nuclear pore proteins Nup88/214 and T-cell acute lymphatic leukemia-associated NUP214 fusion proteins regulate Notch signaling. J Biol Chem. 2019;294:11741-50.
- Mendes A, Fahrenkrog B. NUP214 in leukemia: It's more than transport. Cells. 2019;8:76.
- Scandura JM, Boccuni P, Cammenga J, Nimer SD. Transcription factor fusions in acute leukemia: variations on a theme. Oncogene. 2002;21:3422-44.
- Takeda A, Yaseen NR. Nucleoporins and nucleocytoplasmic transport in hematologic malignancies. Semin Cancer Biol. 2014;27:3-10.
- Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas OA et al. Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia. 2009;23:134–43.
- Bousquet M, Broccardo C, Quelen C, Meggetto F, Kuhlein E, Delsol G et al. A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5. Blood. 2007;109:3417-23.
- Fortschegger K, Anderl S, Denk D, Strehl S. Functional heterogeneity of PAX5 chimeras reveals insight for leukemia development. Mol Cancer Res. 2014;12:595-606.
- Bain BJ, Barnett D, Linch D, Matutes E, Reilly JT. Revised guideline on immunophenotyping in acute leukaemias and chronic lymphoproliferative disorders. Clin Lab Haematol. 2002;24:1–13.
- Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer R, Möricke A et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115:3206-14.
- Kohler A, Hurt E. Gene regulation by nucleoporins and links to cancer. Mol Cell. 2010;38:6–15.
- Chow KH, Factor RE, Ullman KS. The nuclear envelope environment and its cancer connections. Nat Rev Cancer. 2012;12:196–209.
- Kraemer D, Wozniak RW, Blobel G, Radu A. The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm. Proc Natl Acad Sci USA. 1994;91:1519-23.
- Simon DN, Rout MP. Cancer and the nuclear pore complex. Adv Exp Med Biol. 2014;773:285-307.
- Wong RW. New activities of the nuclear pore complexes. Cells. 2021;10:2123.
- Denk D, Bradtke J, König M, Strehl S. PAX5 fusion genes in t(7;9)(q11.2;p13) leukemia: a case report and review of the literatüre. Mol Cytogenet. 2014;7:13.
- Rampello AJ, Laudermilch E, Vishnoi N, Prophet SM, Shao L, Zhao C et al. Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2. J Cell Biol. 2020;219:e201910185.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research |
| Authors | |
| Project Number | TF2013 LTP30 |
| Publication Date | March 31, 2023 |
| Acceptance Date | November 21, 2022 |
| Published in Issue | Year 2023 Volume: 48 Issue: 1 |
