FAT1 Gene Expression in Iranian Acute Lymphoid and Myeloid Leukemia Patients
-
Mohammadreza Ostadali Dehaghi
,
Shahrbano Rostami
,
Ahmadreza Shamshiri
,
Fatemeh Safari
,
Reza Haji Hosseini Haji Hosseini
,
Rick F. Thorne
,
Ardeshir Ghavamzadeh
Abstract
Background: FAT atypical cadherin 1 (FAT1) is a member of the cadherin superfamily whose loss or gain is associated with the initiation and/or progression of different cancers. FAT1 overexpression has been reported in hematological malignancies. This research intended to investigate FAT1 gene expression in adult Iranian acute leukemia patients, compared to normal mobilized peripheral blood CD34+ cells.
Materials and Methods: The peripheral blast (peripheral blood mononuclear cells) cells of 22 acute myeloid leukemia (AML), 14 acute lymphoid leukemia (ALL) patients, and mobilized peripheral blood CD34+ cells of 12 healthy volunteer stem cell donors were collected. Then, quantitative real-time polymerase chain reaction (qPCR) was used to compare FAT1 gene expression.
Results: Overall, there were no significant differences in FAT1 expression between AML and ALL patients (p>0.2). Nonetheless, the mean expression level of FAT1 was significantly higher in leukemic patients (AML and ALL) than in normal CD34+ cells (p=0.029). Additionally, the FAT1 expression levels were significantly higher in both CD34+ and CD34- leukemic patients than in normal CD34+ cells (p=0.028).
Conclusion: No significant differences were found between FAT1 expression in CD34+ and CD34- leukemic samples (p> 0.3). Thus, higher FAT1 expression was evident in ALL and AML leukemia cells but this appeared unrelated to CD34 expression. This suggests in a proportion of adult acute leukemias, FAT1 expression may prove to be a suitable target for therapeutic strategies.
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2. Asai D, Imamura T, Suenobu Si, et al. IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan. Cancer Med. 2013;2(3):412-9.
3 Panagal M, SR S, Gopinathe V, et al. MicroRNA21 and the various types of myeloid leukemia. Cancer Gene Ther. 2018;25(7-8):161-166.
4. Deschler B, Lübbert M. Acute myeloid leukemia: Epidemiology and etiology. Cancer. 2006;107(9):2099-107.
5. Tahmasebi B, Mahmoudi M, Yahya Pour Y, et al. Determination and comparison of incidence rate and trend of morbidity of leukemia and lymphoma in Mazandaran province (1376-1382). J Mazandaran Univ Med Sci. 2006; 16(54):87-89.
6. van den Broek EC, Kater AP, van de Schans SA, et al. Chronic lymphocytic leukaemia in the Netherlands: trends in incidence, treatment and survival, 1989-2008. Eur J Cancer. 2012;48(6):889-95.
7. Thygesen LC, Nielsen OJ, Johansen C. Trends in adult leukemia incidence and survival in Denmark, 1943-2003. Cancer Causes Control. 2009;20(9):1671-80.
8. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.
9. Pallavajjala A, Kim D, Li T, et al. Genomic characterization of chromosome translocations in patients with T/myeloid mixed-phenotype acute leukemia. Leuk Lymphoma. 2018;59(5):1231-1238.
10. Yiau SK, Lee C, Mohd Tohit ER, et al. Potential CD34 signaling through phosphorylated-BAD in chemotherapy-resistant acute myeloid leukemia. J Recept Signal Transduct Res. 2019;39(3):276-282.
11. Jiang Z, Wu D, Lin S, et al. CD34 and CD38 are prognostic biomarkers for acute B lymphoblastic leukemia. Biomark Res. 2016;4:23.
12. Cacciola E, Guglielmo P, Cacciola E, et al. CD34 expression in adult acute lymphoblastic leukemia. Leuk Lymphoma. 1995;18 Suppl 1:31-6.
13. Arber D, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
14. Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103(4):620-5.
15. Lins MM, Mello MJG, Ribeiro RC, et al. Survival and risk factors for mortality in pediatric patients with acute myeloid leukemia in a single reference center in low-middle-income country. Ann Hematol. 2019;98(6):1403-11.
16. Halbleib J, Nelson W. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20(23):3199-214.
17. Sadeqzadeh E, de Bock C, Thorne R. Sleeping giants: emerging roles for the fat cadherins in health and disease. Med Res Rev. 2014;34(1):190-221.
18. Nollet F, Kools P, van Roy F. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol. 2000;299(3):551-72.
19. Ahmed A, de Bock C, Lincz L, et al. FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation. Cell Mol Life SCI. 2015;72(23):4653-69.
20. Zhang X, Liu J, Liang X, et al. History and progression of Fat cadherins in health and disease. Onco Targets Ther. 2016;9:7337-43.
21. de Bock C, Ardjmand A, Molloy T, et al. The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis–relapse samples of precursor B-cell acute lymphoblastic leukemia. Leukemia. 2012;26(5):918–26 .
22. Valletta D, Czech B, Spruss T, et al. Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma. Carcinogenesis. 2014;35(6):1407-15.
23. Wojtalewicz N, Sadeqzadeh E, Weiß JV, et al. A Soluble Form of the Giant Cadherin Fat1 Is Released from Pancreatic Cancer Cells by ADAM10 Mediated Ectodomain Shedding. PLoS ONE. 2014;9(3):e90461.
24. KATOH M. Function and cancer genomics of FAT family genes. Int J Oncol. 2012;41(6):1913.
25. Malik N, Chattopadhyay P, Sarkar C, et al. 70-P Emerging role of FAT1 gene in the regulation of oncogenic miRNA 221/222-3p in glioma. Ann Oncol. 2018;29(suppl 6):vi24.
26. Kwaepila N, Burns G, Leong A. Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis? Pathology. 2006;38(2):125-31.
27. Neumann M, Seehawer M, Schlee C, et al. FAT1 expression and mutations in adult acute lymphoblastic leukemia. Blood Cancer J. 2014;4(6):e224.
28. Gawdat RM, El-Hoseiny SM, Darwish AD, et al. Overexpression of the giant FAT1 cadherin gene and its prognostic significance in de novo acute leukaemia patients. Comp Clin Pathol. 2017;26:505-12.
29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
30. de Bock CE, Down M, Baidya K, et al. T-cell acute lymphoblastic leukemias express a unique truncated FAT1 isoform that cooperates with NOTCH1 in leukemia development. Haematologica. 2019;104(5):e204-e207.
31. Li Y, Lv X, Ge X, et al. Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on nextgeneration sequencing. Mol Med Rep. 2019;19(5):4147-4158.
32. Ardjmand A, Bock CE, Molloy TJ, et al. Altered expression of Fat1 cadherin, a novel tumor marker for acute lymphoblastic leukemia. Clin Biochem. 2011;44(Suppl 13):S71.
33. Ardjmand A, de Bock CE, Shahrokhi S, et al. Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia. Hematology. 2013;18(6):315-22.
34. eumann M, Seehawer M, Schlee C, et al. FAT1 Expression and Mutation Status In Adult Acute Lymphoblastic Leukemia. Blood. 2013;122(21):2564.
35. Dunne J, Hanby AM, Poulsom R, et al. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics. 1995. 20;30(2):207-23.
36. Elmougy MI. Prognostic impact of FAT1 cadherin expression in adult acute lymphoblastic leukemia. Int J Adv Res. 2015:3(10):1489-1496.
37. Garg M, Nagata Y, Kanojia D, et al. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. Blood. 2015;126(22):2491-501.
38. Laginestra MA, Cascione L, Motta G, et al. Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified. Mod Pathol.2020;33 (2):179-187.
39. Morris LG, Kaufman AM, Gong Y, et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat Genet. 2013;45(3):253-61.
40. Cao LL, Riascos-Bernal DF, Chinnasamy P, et al. Control of mitochondrial function and cell growth by the atypical cadherin Fat1. Nature. 2016;539(7630):575-578.
2. Asai D, Imamura T, Suenobu Si, et al. IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan. Cancer Med. 2013;2(3):412-9.
3 Panagal M, SR S, Gopinathe V, et al. MicroRNA21 and the various types of myeloid leukemia. Cancer Gene Ther. 2018;25(7-8):161-166.
4. Deschler B, Lübbert M. Acute myeloid leukemia: Epidemiology and etiology. Cancer. 2006;107(9):2099-107.
5. Tahmasebi B, Mahmoudi M, Yahya Pour Y, et al. Determination and comparison of incidence rate and trend of morbidity of leukemia and lymphoma in Mazandaran province (1376-1382). J Mazandaran Univ Med Sci. 2006; 16(54):87-89.
6. van den Broek EC, Kater AP, van de Schans SA, et al. Chronic lymphocytic leukaemia in the Netherlands: trends in incidence, treatment and survival, 1989-2008. Eur J Cancer. 2012;48(6):889-95.
7. Thygesen LC, Nielsen OJ, Johansen C. Trends in adult leukemia incidence and survival in Denmark, 1943-2003. Cancer Causes Control. 2009;20(9):1671-80.
8. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.
9. Pallavajjala A, Kim D, Li T, et al. Genomic characterization of chromosome translocations in patients with T/myeloid mixed-phenotype acute leukemia. Leuk Lymphoma. 2018;59(5):1231-1238.
10. Yiau SK, Lee C, Mohd Tohit ER, et al. Potential CD34 signaling through phosphorylated-BAD in chemotherapy-resistant acute myeloid leukemia. J Recept Signal Transduct Res. 2019;39(3):276-282.
11. Jiang Z, Wu D, Lin S, et al. CD34 and CD38 are prognostic biomarkers for acute B lymphoblastic leukemia. Biomark Res. 2016;4:23.
12. Cacciola E, Guglielmo P, Cacciola E, et al. CD34 expression in adult acute lymphoblastic leukemia. Leuk Lymphoma. 1995;18 Suppl 1:31-6.
13. Arber D, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
14. Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103(4):620-5.
15. Lins MM, Mello MJG, Ribeiro RC, et al. Survival and risk factors for mortality in pediatric patients with acute myeloid leukemia in a single reference center in low-middle-income country. Ann Hematol. 2019;98(6):1403-11.
16. Halbleib J, Nelson W. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20(23):3199-214.
17. Sadeqzadeh E, de Bock C, Thorne R. Sleeping giants: emerging roles for the fat cadherins in health and disease. Med Res Rev. 2014;34(1):190-221.
18. Nollet F, Kools P, van Roy F. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol. 2000;299(3):551-72.
19. Ahmed A, de Bock C, Lincz L, et al. FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation. Cell Mol Life SCI. 2015;72(23):4653-69.
20. Zhang X, Liu J, Liang X, et al. History and progression of Fat cadherins in health and disease. Onco Targets Ther. 2016;9:7337-43.
21. de Bock C, Ardjmand A, Molloy T, et al. The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis–relapse samples of precursor B-cell acute lymphoblastic leukemia. Leukemia. 2012;26(5):918–26 .
22. Valletta D, Czech B, Spruss T, et al. Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma. Carcinogenesis. 2014;35(6):1407-15.
23. Wojtalewicz N, Sadeqzadeh E, Weiß JV, et al. A Soluble Form of the Giant Cadherin Fat1 Is Released from Pancreatic Cancer Cells by ADAM10 Mediated Ectodomain Shedding. PLoS ONE. 2014;9(3):e90461.
24. KATOH M. Function and cancer genomics of FAT family genes. Int J Oncol. 2012;41(6):1913.
25. Malik N, Chattopadhyay P, Sarkar C, et al. 70-P Emerging role of FAT1 gene in the regulation of oncogenic miRNA 221/222-3p in glioma. Ann Oncol. 2018;29(suppl 6):vi24.
26. Kwaepila N, Burns G, Leong A. Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis? Pathology. 2006;38(2):125-31.
27. Neumann M, Seehawer M, Schlee C, et al. FAT1 expression and mutations in adult acute lymphoblastic leukemia. Blood Cancer J. 2014;4(6):e224.
28. Gawdat RM, El-Hoseiny SM, Darwish AD, et al. Overexpression of the giant FAT1 cadherin gene and its prognostic significance in de novo acute leukaemia patients. Comp Clin Pathol. 2017;26:505-12.
29. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
30. de Bock CE, Down M, Baidya K, et al. T-cell acute lymphoblastic leukemias express a unique truncated FAT1 isoform that cooperates with NOTCH1 in leukemia development. Haematologica. 2019;104(5):e204-e207.
31. Li Y, Lv X, Ge X, et al. Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on nextgeneration sequencing. Mol Med Rep. 2019;19(5):4147-4158.
32. Ardjmand A, Bock CE, Molloy TJ, et al. Altered expression of Fat1 cadherin, a novel tumor marker for acute lymphoblastic leukemia. Clin Biochem. 2011;44(Suppl 13):S71.
33. Ardjmand A, de Bock CE, Shahrokhi S, et al. Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia. Hematology. 2013;18(6):315-22.
34. eumann M, Seehawer M, Schlee C, et al. FAT1 Expression and Mutation Status In Adult Acute Lymphoblastic Leukemia. Blood. 2013;122(21):2564.
35. Dunne J, Hanby AM, Poulsom R, et al. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics. 1995. 20;30(2):207-23.
36. Elmougy MI. Prognostic impact of FAT1 cadherin expression in adult acute lymphoblastic leukemia. Int J Adv Res. 2015:3(10):1489-1496.
37. Garg M, Nagata Y, Kanojia D, et al. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. Blood. 2015;126(22):2491-501.
38. Laginestra MA, Cascione L, Motta G, et al. Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified. Mod Pathol.2020;33 (2):179-187.
39. Morris LG, Kaufman AM, Gong Y, et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat Genet. 2013;45(3):253-61.
40. Cao LL, Riascos-Bernal DF, Chinnasamy P, et al. Control of mitochondrial function and cell growth by the atypical cadherin Fat1. Nature. 2016;539(7630):575-578.
| Files | ||
| Issue | Vol 17, No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v17i2.12644 | |
| Keywords | ||
| FAT1 Cadherin Acute Myeloid Leukemia (AML Acute lymphoid leukemia (ALL) Leukemia | ||
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How to Cite
1.
Ostadali Dehaghi M, Rostami S, Shamshiri A, Safari F, Haji Hosseini RHH, Thorne RF, Ghavamzadeh A. FAT1 Gene Expression in Iranian Acute Lymphoid and Myeloid Leukemia Patients. Int J Hematol Oncol Stem Cell Res. 2023;17(2):81-88.
