RUNX1::RUNX1T1 Fusion in Pediatric Acute Myeloid Leukemia
A Description of Two Cases
Keywords:
Pediatric acute myeloid leukemia, Next Generation Sequencing, RUNX1::RUNX1T1 fusion, Berlin-Frankfurt-Münster (BFM-87) protocol, AML 15 Medical Research Council protocolAbstract
RUNX1::RUNX1T1 is a core-binding factor driving fusion gene which arises from t(8;21)(q22;q22). It is one of the most common chromosomal rearrangements in both pediatric and adult Acute Myeloid Leukemia (AML) with a reported incidence of 15% in children and young adults. There are few case reports documenting RUNX1::RUNX1T1 translocation in pediatric AML. Although this is generally associated with a favorable prognosis, we report two (2) cases of de novo pediatric AML in the Philippines harboring a RUNX1::RUNX1T1 translocation, one eventually relapsed while the other attained remission but succumbed to sepsis.
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References
1. Allen-Rhoades W, Whittle SB, Rainusso N. Pediatric solid tumors in children and adolescents: an overview. Pediatr Rev. 2018;39(9):444-53. https://pubmed.ncbi.nlm.nih.gov/30171055. https://doi.org/10.1542/pir.2017-0268.
2. McPherson RA, Pincus M. Henry’s clinical diagnosis and management by laboratory methods. 23rd ed. Saunders Elsevier; 2016.
3. Swerdlow SH. WHO classification of tumours of haematopoietic and lymphoid tissues Revised 4th ed, vol 2. International Agency for Research on Cancer; 2017.
4. George TI, Bajel A. Diagnosis of rare subtypes of acute myeloid leukaemia and related neoplasms. Pathology. 2021;53(3):312-27. https://pubmed.ncbi.nlm.nih.gov/33676766. https://doi.org/10.1016/j.pathol.2021.02.001.
5. Tamayo SCA, Medalla IMC, Roque EMP, et al. Molecular characterization of acute myeloid leukemia among pediatric Filipino patients using karyotype analysis, fluorescence in situ hybridization and comprehensive next generation sequencing: a multi-center experience [abstract]. In: 35th International Symposium on Technical Innovations in Laboratory Hematology; 2022 Sep 8-10; Bologna, Italy: ISLH; 2022. Abstract number 93.
6. Höllein A, Nadarajah N, Meggendorfer M, et al. Molecular characterization of AML with RUNX1-RUNX1T1 at diagnosis and relapse reveals net loss of co-mutations. Hemasphere. 2019;3(1):e178. https://pubmed.ncbi.nlm.nih.gov/31723813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745937. https://doi.org/10.1097/HS9.0000000000000178.
7. Swart LE, Heidenreich O. The RUNX1/RUNX1T1 network: translating insights into therapeutic options. Exp Hematol. 2021;94:1-10. https://pubmed.ncbi.nlm.nih.gov/33217477. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854360. https://doi.org/10.1016/j.exphem.2020.11.005.
8. Rasche M, Zimmermann M, Borschel L, et al. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia. 2018;32(10):2167-77. https://pubmed.ncbi.nlm.nih.gov/29550834. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170392. https://doi.org/10.1038/s41375-018-0071-7.
9. Hu Y, Chen A, Zheng X, et al. Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy. Natl Sci Rev. 2019;6(3):469-79. https://pubmed.ncbi.nlm.nih.gov/34691895. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291445. https://doi.org/10.1093/nsr/nwz006.
10. Gao L, Tober J, Gao P, Chen C, Tan K, Speck NA. RUNX1 and the endothelial origin of blood. Exp Hematol. 2018;68:2-9. https://pubmed.ncbi.nlm.nih.gov/30391350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494457. https://doi.org/10.1016/j.exphem.2018.10.009.
11. Daniel MG, Rapp K, Schaniel C, Moore KA. Induction of developmental hematopoiesis mediated by transcription factors and the hematopoietic microenvironment. Ann N Y Acad Sci. 2020;1466(1):59-72. https://pubmed.ncbi.nlm.nih.gov/31621095. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162702. https://doi.org/10.1111/nyas.14246.
12. Krauth M-T, Eder C, Alpermann T, et al. High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia. 2014;28(7):1449-58. https://pubmed.ncbi.nlm.nih.gov/24402164. https://doi.org/10.1038/leu.2014.4.
13. Kita K, Nakase K, Miwa H, et al. Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34. Blood. 1992;80(2):470-7. https://pubmed.ncbi.nlm.nih.gov/1378322.
14. Haferlach T, Meggendorfer M. More than a fusion gene: the RUNX1-RUNX1T1 AML. Blood. 2019;133(10):1006-7. https://pubmed.ncbi.nlm.nih.gov/30846508. https://doi.org/10.1182/blood-2019-01-896076.
15. Aung MMK, Mills ML, Bittencourt‐Silvestre J, Keeshan K. Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia. Mol Oncol. 2021;15(9):2253-72. https://pubmed.ncbi.nlm.nih.gov/33421304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410545. https://doi.org/10.1002/1878-0261.12899.
16. Krock B, Oberley MJ. Molecular genetics of pediatric acute myeloid leukemia. Clin Lab Med. 2021;41(3):497-515. https://pubmed.ncbi.nlm.nih.gov/34304778. https://doi.org/10.1016/j.cll.2021.03.014.
17. Reinhardt D, Antoniou E, Waack K. Pediatric acute myeloid leukemia—past, present, and future. J Clin Med. 2022;11(3):504. https://pubmed.ncbi.nlm.nih.gov/35159956. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837075. https://doi.org/10.3390/jcm11030504.
18. Totadri S, Bhatia P, Sreedharanunni S. RUNX1-RUNX1T1-positive acute myeloid leukaemia presenting as bilateral proptosis and multiple cranial nerve palsy. BMJ Case Rep. 2017;2017:bcr2017221402. https://pubmed.ncbi.nlm.nih.gov/28993357. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652363. https://doi.org/10.1136/bcr-2017-221402.
19. Kondo H, Kanayama T, Matsumura U, et al. Relapsed RUNX1-RUNX1T1-positive acute myeloid leukemia with pseudo-Chediak-Higashi granules. Int J Hematol. 2021;113(5):616-7. https://pubmed.ncbi.nlm.nih.gov/33782817. https//doi.org/10.1007/s12185-021-03141-7.
20. Wei H, Liu X, Wang Y, et al. Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1–RUNX1T1. Exp Hematol. 2021;96:63-72.e3. https://pubmed.ncbi.nlm.nih.gov/33524443 . https://doi.org/10.1016/j.exphem.2021.01.007.
21. Höllein A, Jeromin S, Meggendorfer M, et al. Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients. Leukemia. 2018;32(10):2270-4. https://pubmed.ncbi.nlm.nih.gov/29568097. https://doi.org/10.1038/s41375-018-0086-0.
22. Higgins A, Shah MV. Genetic and genomic landscape of secondary and therapy-related acute myeloid leukemia. Genes (Basel). 2020;11(7):749. https://pubmed.ncbi.nlm.nih.gov/32640569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397259. https://doi.org/10.3390/genes11070749.
23. Feng Y, Li X, Cassady K, Zou Z, Zhang X. TET2 function in hematopoietic malignancies, immune regulation, and DNA repair. Front Oncol. 2019;9:210. https://pubmed.ncbi.nlm.nih.gov/31001476. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454012. https://doi.org/10.3389/fonc.2019.00210.
24. Badr P, Elsayed GM, Eldin DN, Riad BY, Hamdy N. Detection of KIT mutations in core binding factor acute myeloid leukemia. Leuk Res Rep. 2018;10:20-5. https://pubmed.ncbi.nlm.nih.gov/30112273. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092444. https://doi.org/10.1016/j.lrr.2018.06.004.
25. Ghafoor T, Khalil S, Farah T, Ahmed S, Sharif I. Prognostic factors in childhood acute myeloid leukemia; experience from a developing country. Cancer Rep (Hoboken). 2020;3(5):e1259. https://pubmed.ncbi.nlm.nih.gov/33085844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941425. https://doi.org/10.1002/cnr2.1259.
2. McPherson RA, Pincus M. Henry’s clinical diagnosis and management by laboratory methods. 23rd ed. Saunders Elsevier; 2016.
3. Swerdlow SH. WHO classification of tumours of haematopoietic and lymphoid tissues Revised 4th ed, vol 2. International Agency for Research on Cancer; 2017.
4. George TI, Bajel A. Diagnosis of rare subtypes of acute myeloid leukaemia and related neoplasms. Pathology. 2021;53(3):312-27. https://pubmed.ncbi.nlm.nih.gov/33676766. https://doi.org/10.1016/j.pathol.2021.02.001.
5. Tamayo SCA, Medalla IMC, Roque EMP, et al. Molecular characterization of acute myeloid leukemia among pediatric Filipino patients using karyotype analysis, fluorescence in situ hybridization and comprehensive next generation sequencing: a multi-center experience [abstract]. In: 35th International Symposium on Technical Innovations in Laboratory Hematology; 2022 Sep 8-10; Bologna, Italy: ISLH; 2022. Abstract number 93.
6. Höllein A, Nadarajah N, Meggendorfer M, et al. Molecular characterization of AML with RUNX1-RUNX1T1 at diagnosis and relapse reveals net loss of co-mutations. Hemasphere. 2019;3(1):e178. https://pubmed.ncbi.nlm.nih.gov/31723813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745937. https://doi.org/10.1097/HS9.0000000000000178.
7. Swart LE, Heidenreich O. The RUNX1/RUNX1T1 network: translating insights into therapeutic options. Exp Hematol. 2021;94:1-10. https://pubmed.ncbi.nlm.nih.gov/33217477. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854360. https://doi.org/10.1016/j.exphem.2020.11.005.
8. Rasche M, Zimmermann M, Borschel L, et al. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia. 2018;32(10):2167-77. https://pubmed.ncbi.nlm.nih.gov/29550834. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170392. https://doi.org/10.1038/s41375-018-0071-7.
9. Hu Y, Chen A, Zheng X, et al. Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy. Natl Sci Rev. 2019;6(3):469-79. https://pubmed.ncbi.nlm.nih.gov/34691895. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291445. https://doi.org/10.1093/nsr/nwz006.
10. Gao L, Tober J, Gao P, Chen C, Tan K, Speck NA. RUNX1 and the endothelial origin of blood. Exp Hematol. 2018;68:2-9. https://pubmed.ncbi.nlm.nih.gov/30391350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494457. https://doi.org/10.1016/j.exphem.2018.10.009.
11. Daniel MG, Rapp K, Schaniel C, Moore KA. Induction of developmental hematopoiesis mediated by transcription factors and the hematopoietic microenvironment. Ann N Y Acad Sci. 2020;1466(1):59-72. https://pubmed.ncbi.nlm.nih.gov/31621095. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162702. https://doi.org/10.1111/nyas.14246.
12. Krauth M-T, Eder C, Alpermann T, et al. High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia. 2014;28(7):1449-58. https://pubmed.ncbi.nlm.nih.gov/24402164. https://doi.org/10.1038/leu.2014.4.
13. Kita K, Nakase K, Miwa H, et al. Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34. Blood. 1992;80(2):470-7. https://pubmed.ncbi.nlm.nih.gov/1378322.
14. Haferlach T, Meggendorfer M. More than a fusion gene: the RUNX1-RUNX1T1 AML. Blood. 2019;133(10):1006-7. https://pubmed.ncbi.nlm.nih.gov/30846508. https://doi.org/10.1182/blood-2019-01-896076.
15. Aung MMK, Mills ML, Bittencourt‐Silvestre J, Keeshan K. Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia. Mol Oncol. 2021;15(9):2253-72. https://pubmed.ncbi.nlm.nih.gov/33421304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410545. https://doi.org/10.1002/1878-0261.12899.
16. Krock B, Oberley MJ. Molecular genetics of pediatric acute myeloid leukemia. Clin Lab Med. 2021;41(3):497-515. https://pubmed.ncbi.nlm.nih.gov/34304778. https://doi.org/10.1016/j.cll.2021.03.014.
17. Reinhardt D, Antoniou E, Waack K. Pediatric acute myeloid leukemia—past, present, and future. J Clin Med. 2022;11(3):504. https://pubmed.ncbi.nlm.nih.gov/35159956. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837075. https://doi.org/10.3390/jcm11030504.
18. Totadri S, Bhatia P, Sreedharanunni S. RUNX1-RUNX1T1-positive acute myeloid leukaemia presenting as bilateral proptosis and multiple cranial nerve palsy. BMJ Case Rep. 2017;2017:bcr2017221402. https://pubmed.ncbi.nlm.nih.gov/28993357. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652363. https://doi.org/10.1136/bcr-2017-221402.
19. Kondo H, Kanayama T, Matsumura U, et al. Relapsed RUNX1-RUNX1T1-positive acute myeloid leukemia with pseudo-Chediak-Higashi granules. Int J Hematol. 2021;113(5):616-7. https://pubmed.ncbi.nlm.nih.gov/33782817. https//doi.org/10.1007/s12185-021-03141-7.
20. Wei H, Liu X, Wang Y, et al. Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1–RUNX1T1. Exp Hematol. 2021;96:63-72.e3. https://pubmed.ncbi.nlm.nih.gov/33524443 . https://doi.org/10.1016/j.exphem.2021.01.007.
21. Höllein A, Jeromin S, Meggendorfer M, et al. Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients. Leukemia. 2018;32(10):2270-4. https://pubmed.ncbi.nlm.nih.gov/29568097. https://doi.org/10.1038/s41375-018-0086-0.
22. Higgins A, Shah MV. Genetic and genomic landscape of secondary and therapy-related acute myeloid leukemia. Genes (Basel). 2020;11(7):749. https://pubmed.ncbi.nlm.nih.gov/32640569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397259. https://doi.org/10.3390/genes11070749.
23. Feng Y, Li X, Cassady K, Zou Z, Zhang X. TET2 function in hematopoietic malignancies, immune regulation, and DNA repair. Front Oncol. 2019;9:210. https://pubmed.ncbi.nlm.nih.gov/31001476. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454012. https://doi.org/10.3389/fonc.2019.00210.
24. Badr P, Elsayed GM, Eldin DN, Riad BY, Hamdy N. Detection of KIT mutations in core binding factor acute myeloid leukemia. Leuk Res Rep. 2018;10:20-5. https://pubmed.ncbi.nlm.nih.gov/30112273. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092444. https://doi.org/10.1016/j.lrr.2018.06.004.
25. Ghafoor T, Khalil S, Farah T, Ahmed S, Sharif I. Prognostic factors in childhood acute myeloid leukemia; experience from a developing country. Cancer Rep (Hoboken). 2020;3(5):e1259. https://pubmed.ncbi.nlm.nih.gov/33085844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941425. https://doi.org/10.1002/cnr2.1259.
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Published
2023-02-25
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Jaime, J., Medalla, I. M., Tamayo, S. C., Pido, Q., Tria IV, F., Enriquez, M. L., … Ang, D. (2023). RUNX1::RUNX1T1 Fusion in Pediatric Acute Myeloid Leukemia: A Description of Two Cases. PJP. Retrieved from https://philippinejournalofpathology.org/index.php/PJP/article/view/359
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