Detection of T315I Mutation in Ph+ Leukemias: Clinical Insights from One Case Report

Jaramillo Jaramillo, Carolina; Pérez Mejía, Juliana; Rave Zapata, Sara María; Villa Palacio, Maria Isabel; Velasco Cardona, Diana Carolina

doi:10.61882/ijbc.17.3.5

Volume 17, Issue 3 (September-2025 2025) Iranian Journal of Blood and Cancer 2025, 17(3): 5-13 | Back to browse issues page

‎ 10.61882/ijbc.17.3.5

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Jaramillo Jaramillo C, Pérez Mejía J, Rave Zapata S M, Villa Palacio M I, Velasco Cardona D C. Detection of T315I Mutation in Ph+ Leukemias: Clinical Insights from One Case Report. Iranian Journal of Blood and Cancer 2025; 17 (3) :5-13
URL: http://ijbc.ir/article-1-1770-en.html

Detection of T315I Mutation in Ph+ Leukemias: Clinical Insights from One Case Report

Carolina Jaramillo Jaramillo¹

, Juliana Pérez Mejía²

, Sara María Rave Zapata³

, Maria Isabel Villa Palacio⁴

, Diana Carolina Velasco Cardona ^*⁵

1- School of Bacteriology, Colegio Mayor de Antioquia, Colombia.
2- Health Sciences, Colegio Mayor de Antioquia, Colombia.
3- Antioquia, Colegio Mayor de Antioquia, Colombia.
4- Faculty of Health Sciences, Colegio Mayor de Antioquia, Colombia.
5- Health Sciences, Colegio Mayor de Antioquia, Colombia. , dcvelasco@est.colmayor.edu.co

Abstract: (429 Views)

The reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, results in the formation of the BCR/ABL fusion gene. This genetic aberration leads to dysregulation of intracellular kinase activity. The detection of the Philadelphia chromosome is a critical component of the diagnostic evaluation of myeloproliferative neoplasms and acute lymphoid leukemia. In treatments involving tyrosine kinase inhibitors, at least 70 genetic variants have been documented as factors that induce resistance to drugs. This includes the T315I mutation, which has been identified as the most prevalent in multiple countries and is of significant clinical significance. This mutation is detected in patients who have experienced therapeutic failure, thereby significantly restricting the available treatment options. In Colombia, the prevalence of this mutation and the dynamics of its appearance are not yet fully understood. Furthermore, there is a paucity of information regarding the management and prognosis of patients who express the mutation. In this study, the genomic DNA of 26 patients with Philadelphia chromosome was analyzed using the real-time molecular technique PCR. The objective was to identify the T315I genetic variant, which was positive in two of the patients diagnosed with CML. We present a case of a 39-year-old female patient diagnosed with Ph+ CML who exhibited resistance to treatment and detection of this mutation.

Keywords: Chronic myeloproliferative neoplasm, Philadelphia chromosome, BCR/ABL.

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: Original Article | Subject: Adults Hematology & Oncology
Received: 2025/07/14 | Accepted: 2025/09/11 | Published: 2025/09/30

References

1. Lim MS, Leval L, Quintanilla-Martinez L. Commentary on The 2008 WHO classification of mature T- and NK-cell neoplasms. J Hematop. 2009;2(2). [DOI:10.1007/s12308-009-0034-z]

2. Lloyd R V. Hematopathology. In: Pathology: Historical and Contemporary Aspects. Cham: Springer; 2023. [DOI:10.1007/978-3-031-39554-3]

3. Zhang L, Liu Y, Wang L, Wang L, Zheng L, He W, et al. A novel research model of clonal evolution in mantle cell lymphoma at the single-cell genomic level. Genes Dis. 2025;12(3):101406. [DOI:10.1016/j.gendis.2024.101406]

4. Moura MC, Davalos V, Planas-Serra L, Alvarez-Errico D, Arribas C, Ruiz M, et al. Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine. 2021;66. [DOI:10.1016/j.ebiom.2021.103339]

5. Pérez Mejía J, Acevedo Toro P. Epigenética: una nueva herramienta para el estudio de la leucemia mieloide crónica TT - Epigenetics: a new tool for the study of chronic myeloid leukemia. 2013.

6. Aspa-Cilleruelo JM, de Hontanar Torres GL, Gómez MM, Mazo EM. Neoplasias mieloproliferativas crónicas. Clasificación. Leucemia mieloide crónica. Medicine - Programa de Formación Médica Continuada Acreditado. 2024 Nov;14(20):1149-56. [DOI:10.1016/j.med.2024.10.019]

7. Roychowdhury S, Talpaz M. Managing resistance in chronic myeloid leukemia. Blood Rev. 2011;25(6). [DOI:10.1016/j.blre.2011.09.001]

8. Minciacchi VR, Kumar R, Krause DS. Chronic myeloid leukemia: a model disease of the past, present and future. Cells. 2021;10(1):117. [DOI:10.3390/cells10010117]

9. Nguyen T, Harama D, Tamai M, Kagami K, Komatsu C, Kasai S, et al. Synergistic effect of asciminib with reduced doses of ponatinib in human Ph+ myeloid leukemia with the T315M mutation. Int J Hematol. 2025;1-11. [DOI:10.1007/s12185-025-03981-7]

10. Lavallade King's College London H. Chronic myeloid leukaemia. Medicine. 2013 May; [DOI:10.1016/j.mpmed.2013.03.001]

11. Morales C, Cárdenas V, Valencia JE, Ribón G, Manrique R. Leucemia mieloide crónica: diagnóstico y tratamiento TT - Chronic myeloid leukemia: diagnosis and treatment. CES Medicina. 2010;24(1).

12. Zhang Y, Rowley JD. Chronic myeloid leukemia: Current perspectives. 2011. [DOI:10.1016/j.cll.2011.08.012]

13. Valencia-Serna J, Gul-Uludaǧ H, Mahdipoor P, Jiang X, Uludaǧ H. Investigating siRNA delivery to chronic myeloid leukemia K562 cells with lipophilic polymers for therapeutic BCR-ABL down-regulation. Journal of Controlled Release. 2013;172(2). [DOI:10.1016/j.jconrel.2013.05.014]

14. Liu-Dumlao T, Kantarjian H, Thomas DA, O'Brien S, Ravandi F. Philadelphia-positive acute lymphoblastic leukemia: Current treatment options. Curr Oncol Rep. 2012;14(5). [DOI:10.1007/s11912-012-0247-7]

15. Enrico A, Leukemia MJAL. Philadelphia Positive (Ph1) (Incidence Classifications, Prognostic Factor in ALL Principles of ALL Therapy. In: Clinical Epidemiology of Acute Lymphoblastic Leukemia - From the Molecules to the Clinic. 2013. [DOI:10.5772/55095]

16. Adesanya AE. Characterization of T315I BCR-ABL1-mediated drug resistance in chronic myeloid leukemia: new regulatory mechanism and clinical detection assay. 2024.

17. Shafi O, Rajpar R, Kanwal F, Waqas M, Khan OJ, Raveena, et al. Leukemogenesis in Acute Lymphoblastic Leukemia through the Lens of Developmental Dynamics of Lymphoid Progenitor Cells: a systematic review [Internet]. 2024. Available from: [DOI:10.1101/2024.07.14.24310322]

18. Baer C, Meggendorfer M, Haferlach C, Kern W, Haferlach T. Detection of ABL1 kinase domain mutations in therapy-naïve BCR-ABL1-positive acute lymphoblastic leukemia. Haematologica. 2021;107(2):562. [DOI:10.3324/haematol.2021.279807]

19. Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243(5405). [DOI:10.1038/243290a0]

20. Cortes J, Kantarjian H. Advanced-phase chronic myeloid leukemia. 2003. [DOI:10.1053/shem.2003.50005]

21. Al-Ali HK, Heinrich MC, Lange T, Krahl R, Mueller M, Müller C. High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematology Journal. 2004;5(1). [DOI:10.1038/sj.thj.6200319]

22. Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B. Nilotinib in Imatinib-Resistant CML and Philadelphia Chromosome-Positive ALL. New England Journal of Medicine. 2006;354(24). [DOI:10.1056/NEJMoa055104]

23. Roche-Lestienne C, Soenen-Cornu V, Grardel-Duflos N, Laï JL, Philippe N, Facon T. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood. 2002;100(3). [DOI:10.1182/blood.V100.3.1014]

24. BJ RDR, CL HSA, HK AA, DJ ERE, SF OERE, JM OFO. Activity of a Specific Inhibitor of the Bcr-Abl Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia With the Philadelphia Chromosome. N Engl J Med. 1038;344(14). [DOI:10.1056/NEJM200104053441402]

25. O'Dwyer ME, Mauro MJ, Kurilik G, Mori M, Balleisen S, Olson S. The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood. 2002;100(5). [DOI:10.1182/blood-2002-03-0777]

26. Cervantes F, Hernández-Boluda JC, Steegmann JL, Conde E, Alvarez-Larrán A, López-Jiménez J. Imatinib mesylate therapy of chronic phase chronic myeloid leukemia resistant or intolerant to interferon: Results and prognostic factors for response and progression-free survival in 150 patients. Haematologica. 2003;88(10).

27. Mian AA, Haberbosch I, Khamaisie H, Agbarya A, Pietsch L, Eshel E, et al. Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K. Ann Hematol. 2021;100(8):2023-9. [DOI:10.1007/s00277-020-04357-z]

28. Navath S, Navath PA. Advances in the Treatment of Ph+ Chronic Myeloid Leukemia: A Comprehensive Study. International Journal of Cancer Therapeutics. 2024;1(1):37-41. https://doi.org/10.55124/jct.v1i1.235 [DOI:10.55124/jct.v1i1.236]

29. Miething C, Feihl S, Mugler C, Grundler R, Bubnoff N, Lordick F. The Bcr-Abl mutations T315I and Y253H do not confer a growth advantage in the absence of imatinib. Leukemia. 2006;20(4). [DOI:10.1038/sj.leu.2404151]

30. Liu J, Zhang Y, Huang H, Lei X, Tang G, Cao X, et al. Recent advances in Bcr‐Abl tyrosine kinase inhibitors for overriding T315I mutation. Chem Biol Drug Des. 2021;97(3):649-64. [DOI:10.1111/cbdd.13801]

31. Breccia M, Abruzzese E, Castagnetti F, Bonifacio M, Gangemi D, Sorà F, et al. Ponatinib as second-line treatment in chronic phase chronic myeloid leukemia patients in real-life practice. Ann Hematol. 2018 Sep 19;97(9):1577-80. [DOI:10.1007/s00277-018-3337-2]

32. Polo VA, Sossa C, Boquimpani C, Salazar LA, Munevar I, Gómez R, et al. Real World Evidence From 2 Decades of First-Line TKI Therapy in Chronic Myeloid Leukemia (CML): Insights From ACHO's RENEHOC Registry. Clin Lymphoma Myeloma Leuk. 2025;25(5):290- 301. [DOI:10.1016/j.clml.2024.12.015]

33. Vásquez Palacio G, Ramírez GC, Muskus CE, Torres JD, Aya CA. Detección de mutaciones en el dominio tirosina quinasa de BCR-ABL1 en pacientes colombianos con leucemia mieloide crónica LMC, resistentes al imatinib. Revista Colombiana de Cancerología. 2018 Jan;22(1):8-17. [DOI:10.1016/j.rccan.2018.02.001]

34. Yolima Méndez-Camacho, Mónica Giraldo-Castaño, María Fernanda Rocha. Identification of emotional and social needs and access to health services of patients diagnosed with Chronic Myeloid Leukemia in Colombia. RevColHematolOncol. 2021;8(1):10-7.

35. Osman AEG, Deininger MW. Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions. Blood Rev. 2021;49. [DOI:10.1016/j.blre.2021.100825]

36. Tadesse F, Asres G, Abubeker A, Gebremedhin A, Radich J. Spectrum of BCR-ABL Mutations and Treatment Outcomes in Ethiopian Imatinib-Resistant Patients With Chronic Myeloid Leukemia. JCO Glob Oncol. 2021; [DOI:10.1200/GO.21.00058]

37. Bahram C, Zaker F, Mousavi SA, Kazemi A, Ostadali M, Nadali F. Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance. Hematology. 2013;18(3). [DOI:10.1179/1607845412Y.0000000050]

38. Shih LY, Kuo MC, Kuo CY, Lin TH, Bai LY, Chen TY. Emerging kinetics of BCR-ABL1 mutations and their effect on disease outcomes in chronic myeloid leukemia patients with imatinib failure. Leuk Res. 2013;37(1). [DOI:10.1016/j.leukres.2012.09.012]

39. Li B, Brady SW, Ma X, Shen S, Zhang Y, Li Y. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. Blood. 2020;135(1).

40. Khorashad JS, Kelley TW, Szankasi P, Mason CC, Soverini S, Adrian LT. BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: Frequency and clonal relationships. Blood. 2013;121(3). [DOI:10.1182/blood-2012-05-431379]

41. Izzo B, Gottardi EM, Errichiello S, Daraio F, Baratè C, Galimberti S. Monitoring Chronic Myeloid Leukemia: How Molecular Tools May Drive Therapeutic Approaches. 2019. [DOI:10.3389/fonc.2019.00833]

42. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. 2006. [DOI:10.1182/blood-2006-01-0092]

43. Liu J, Yang H, Xu X, Yi S, Meng L. Mutations in the bcr-abl1 kinase domain in patients with chronic myeloid leukaemia treated with tkis or at diagnosis. Oncol Lett. 2020;20(2). [DOI:10.3892/ol.2020.11650]

44. Khair HE, Mohamed BA, Nour BY, Waggiallah HA. Prevalence of BCR-ABL T315I Mutation in Different Chronic Myeloid Leukemia patients Categories. Pakistan Journal of Biological Sciences. 2022;25(2). [DOI:10.3923/pjbs.2022.175.181]

45. Kim WS, Kim D, Kim DW, Kweon IY, Kim SH, Goh HG. Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors. Hematol Oncol. 2010;28(2). [DOI:10.1002/hon.918]

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