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P210 breakpoint is associated with less minimal residual disease compared to p190 breakpoint in acute lymphoblastic leukemia patients with Philadelphia chromosome

Year 2020, Volume: 3 Issue: 3, 307 - 311, 18.06.2020
https://doi.org/10.32322/jhsm.735979

Abstract

Introduction: The Philadelphia chromosome is the most common cytogenetic abnormality in adult patients with acute lymphoblastic leukemia. In addition to its role in treatment choice, evaluation of Philadelphia chromosome is also important to monitor the minimal residual disease. In this study, we aim to study the differences of minimal residual disease status between 2 breakpoint regions (p190 and p210) in adult patients with acute lymphoblastic leukemia.
Material and Method: The data of 205 acute lymphoblastic leukemia patients whose genetic evaluations were performed at our center between March 2010 and February 2019 were retrospectively analyzed.
Results: Philadelphia chromosome was observed in 30 (14.6%) patients. In 75% of the patients who had p210 breakpoint at the time of diagnosis, minimal residual disease was negative after 2 cycles of chemotherapy whereas only 42.8% of the patients who had p190 at the time of diagnosis, minimal residual disease was negative after 2 cycles of chemotherapy. The frequency of Philadelphia chromosome was the highest in 51-60 years age group and it was the least in 18-39 age group in adult B cell acute lymphoblastic leukemia patients.
Conclusion: To the best of our knowledge, this is the first study which evaluated the minimal residual disease status of Philadelphia positive acute lymphoblastic leukemia patients by classifying them into 2 groups according to 2 breakpoints (p190 and p210) in the BCR locus. In our study, we found that p190 breakpoint is associated with less minimal residual disease negative status compared to the patients with p210 breakpoint, therefore more augmented therapies may be preferred in patients with p190 breakpoint compared to therapies of patients with p210 breakpoint.

References

  • 1. Fey MF, Buske C. Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24: vi138-43.
  • 2. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J 2016; 6: e441.
  • 3. Bartram CR, de Klein A, Hagemeijer A, et al. Translocation of c-ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 1983; 306: 277-80.
  • 4. Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc 2005; 80: 1517-27.
  • 5. Usvasalo A, Räty R, Harila-Saari A, et al. Acute lymphoblastic leukemias with normal karyotypes are not without genomic aberrations. Cancer Genet Cytogenet 2009; 192: 10-7.
  • 6. Pui CH, Relling MV, Downing JR, Acute lymphoblastic leukemia. N Engl J Med 2004; 350: 1535-48.
  • 7. Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet 1998; 32: 495-519.
  • 8. Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005; 23: 6306-15.
  • 9. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 1999; 354: 1499–503.
  • 10. Roberts KG, Mullighan CG. Genomics in acute lymphoblastic leukaemia: insights and treatment implications. Nat Rev Clin Oncol 2015; 12: 344– 57.
  • 11. Bacher U, Kohlmann A, Haferlach T. Gene expression profiling for diagnosis and therapy in acute leukaemia and other haematologic malignancies. Cancer Treat Rev 2010; 36: 637-46.
  • 12. Bungaro S, Dell’Orto MC, Zangrando A, et al. Integration of genomic and gene expression data of childhood ALL with‐ out known aberrations identifies subgroups with specific genetic hallmarks. Genes Chromosomes Cancer 2009; 48: 22-38.
  • 13. Iacobucci I, Mullighan C. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol 2017; 35: 975-83.
  • 14. 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: 2391-405
  • 15. Wetzler M, Dodge RK, Mrozek K, et al. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 1999; 93: 3983–93.
  • 16. Faderl S, Jeha S, Kantarjian HM. The biology and therapy of adult acute lymphoblastic leukemia. Cancer 2003; 98: 1337–54.
  • 17. Burmeister T, Schwartz S, Bartram CR, Gokbuget N, Hoelzer D, Thiel E. Patients’ age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 2008; 112: 918–9.
  • 18. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 1991; 5: 196–9.
  • 19. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354: 166–78.
  • 20. Downing JR, Shannon KM. Acute leukemia: a pediatric perspective. Cancer Cell 2002; 2: p.437-45.
  • 21. Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290–3.
  • 22. Teitell MA, Pandolfi PP. Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol 2009; 4: 175-98.
  • 23. Nashed AL, Rao KW, Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagn 2003; 5: 63-72.
  • 24. Gleissner B, Gokbuget N, Bartram CR, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002; 99: 1536–43.
  • 25. Vitale A, Guarini A, Chiaretti S, Foa R. The changing scene of adult acute lymphoblastic leukemia. Curr Opin Oncol 2006; 18: 652–9.
  • 26. Jaso J, Thomas DA, Cunningham K, et al. Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive b-lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Cancer 2011; 117: 4009–17
  • 27. Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. Cancer 2008; 112: 416–32.
  • 28. Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 2011; 29: 532–43.
  • 29. Mullighan CG. New strategies in acute lymphoblastic leukemia: translating advances in genomics into clinical practice. Clin Cancer Res 2011; 17: 396–400.
  • 30. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960; 25: 85-109.
  • 31. Ravandi F. How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood 2019; 133: 130-6. (doi: 10.1182/blood-2018-08-832105).
  • 32. de França Azevedo I, da Silva Júnior RM, de Vasconcelos AV, et al. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia. Rev Bras Hematol Hemoter 2014; 36: 351–5.
  • 33. Dombret H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia results of the prospective multicenter LALA-94 trial. Blood 2002; 100: 2357–66.

Philadelphia kromozomu olan akut lenfoblastik lösemi hastalarında p210 kırılma noktası P190 kırılma noktasına göre daha az minimal kalıntı hastalığı ile ilişkilidir

Year 2020, Volume: 3 Issue: 3, 307 - 311, 18.06.2020
https://doi.org/10.32322/jhsm.735979

Abstract

Giriş: Philadelphia kromozomu, akut lenfoblastik lösemili erişkin hastalarda en sık görülen sitogenetik anormalliktir. Philadelphia kromozomunun değerlendirilmesi, tedavi seçimindeki rolüne ek olarak minimal rezidüel hastalığı izlemek için önemlidir. Bu çalışmada akut lenfoblastik lösemili yetişkin hastalarda 2 kırılma noktası (p190 ve p210) arasındaki minimal rezidüel hastalığı durumu farklılıklarını araştırmayı amaçladık.
Gereç ve Yöntem: Mart 2010-Şubat 2019 tarihleri arasında merkezimizde genetik tetkikleri yapılan 205 akut lenfoblastik lösemili hastasının verileri retrospektif olarak incelendi.
Bulgular: 30 hastada (%14,6) Philadelphia kromozomu gözlendi. Tanı anında p210 kırılma noktası olan hastaların %75’inde 2 siklus kemoterapi sonrasında minimal rezidüel hastalığı negatif hale gelirken, tanı anında p190 kırılma noktası olan hastaların sadece %42,8’inde 2 siklus kemoterapi sonrasında minimal rezidüel hastalığı negatif hale geldi. Philadelphia kromozomu sıklığı 51-60 yaş grubunda en yüksek, 18-39 yaş grubunda en az idi.
Sonuç: Literatür taramamıza göre bu çalışma, Philadelphia pozitif akut lenfoblastik lösemili hastalarının minimal rezidüel hastalığı durumunu kırılma noktalarına göre (p190 ve p210) 2 gruba ayırarak değerlendiren ilk çalışmadır. Çalışmamızda BCR lokusundaki p190 kırılma noktasının, p210 kırılma noktasına sahip hastalara kıyasla daha az minimal rezidüel hastalığı negatif durum ile ilişkili olduğunu bulduk, bu nedenle p190 kırılma noktası olan hastalarda p210 kırılma noktası olan hastalarda kullanılan tedavilere kıyasla daha fazla yoğun tedaviler tercih edilebilir.

References

  • 1. Fey MF, Buske C. Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24: vi138-43.
  • 2. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J 2016; 6: e441.
  • 3. Bartram CR, de Klein A, Hagemeijer A, et al. Translocation of c-ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 1983; 306: 277-80.
  • 4. Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc 2005; 80: 1517-27.
  • 5. Usvasalo A, Räty R, Harila-Saari A, et al. Acute lymphoblastic leukemias with normal karyotypes are not without genomic aberrations. Cancer Genet Cytogenet 2009; 192: 10-7.
  • 6. Pui CH, Relling MV, Downing JR, Acute lymphoblastic leukemia. N Engl J Med 2004; 350: 1535-48.
  • 7. Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet 1998; 32: 495-519.
  • 8. Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005; 23: 6306-15.
  • 9. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 1999; 354: 1499–503.
  • 10. Roberts KG, Mullighan CG. Genomics in acute lymphoblastic leukaemia: insights and treatment implications. Nat Rev Clin Oncol 2015; 12: 344– 57.
  • 11. Bacher U, Kohlmann A, Haferlach T. Gene expression profiling for diagnosis and therapy in acute leukaemia and other haematologic malignancies. Cancer Treat Rev 2010; 36: 637-46.
  • 12. Bungaro S, Dell’Orto MC, Zangrando A, et al. Integration of genomic and gene expression data of childhood ALL with‐ out known aberrations identifies subgroups with specific genetic hallmarks. Genes Chromosomes Cancer 2009; 48: 22-38.
  • 13. Iacobucci I, Mullighan C. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol 2017; 35: 975-83.
  • 14. 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: 2391-405
  • 15. Wetzler M, Dodge RK, Mrozek K, et al. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 1999; 93: 3983–93.
  • 16. Faderl S, Jeha S, Kantarjian HM. The biology and therapy of adult acute lymphoblastic leukemia. Cancer 2003; 98: 1337–54.
  • 17. Burmeister T, Schwartz S, Bartram CR, Gokbuget N, Hoelzer D, Thiel E. Patients’ age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 2008; 112: 918–9.
  • 18. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 1991; 5: 196–9.
  • 19. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006; 354: 166–78.
  • 20. Downing JR, Shannon KM. Acute leukemia: a pediatric perspective. Cancer Cell 2002; 2: p.437-45.
  • 21. Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290–3.
  • 22. Teitell MA, Pandolfi PP. Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol 2009; 4: 175-98.
  • 23. Nashed AL, Rao KW, Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagn 2003; 5: 63-72.
  • 24. Gleissner B, Gokbuget N, Bartram CR, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002; 99: 1536–43.
  • 25. Vitale A, Guarini A, Chiaretti S, Foa R. The changing scene of adult acute lymphoblastic leukemia. Curr Opin Oncol 2006; 18: 652–9.
  • 26. Jaso J, Thomas DA, Cunningham K, et al. Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive b-lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Cancer 2011; 117: 4009–17
  • 27. Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. Cancer 2008; 112: 416–32.
  • 28. Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 2011; 29: 532–43.
  • 29. Mullighan CG. New strategies in acute lymphoblastic leukemia: translating advances in genomics into clinical practice. Clin Cancer Res 2011; 17: 396–400.
  • 30. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960; 25: 85-109.
  • 31. Ravandi F. How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood 2019; 133: 130-6. (doi: 10.1182/blood-2018-08-832105).
  • 32. de França Azevedo I, da Silva Júnior RM, de Vasconcelos AV, et al. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia. Rev Bras Hematol Hemoter 2014; 36: 351–5.
  • 33. Dombret H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia results of the prospective multicenter LALA-94 trial. Blood 2002; 100: 2357–66.
There are 33 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Article
Authors

Tuğçe Nur Yiğenoğlu 0000-0001-9962-8882

Taha Bahsi 0000-0001-7210-7374

Haktan Erdem 0000-0002-4391-1387

Neslihan Duzkale 0000-0001-6122-5316

Bahar Uncu Ulu 0000-0002-6230-9519

Dicle İskender 0000-0002-6062-6422

Merih Kızıl Çakır 0000-0003-0978-0923

Sinan Dal 0000-0002-5994-2735

Fevzi Altuntaş 0000-0001-6872-3780

Publication Date June 18, 2020
Published in Issue Year 2020 Volume: 3 Issue: 3

Cite

AMA Yiğenoğlu TN, Bahsi T, Erdem H, Duzkale N, Uncu Ulu B, İskender D, Kızıl Çakır M, Dal S, Altuntaş F. P210 breakpoint is associated with less minimal residual disease compared to p190 breakpoint in acute lymphoblastic leukemia patients with Philadelphia chromosome. J Health Sci Med / JHSM. June 2020;3(3):307-311. doi:10.32322/jhsm.735979

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