Display options
Share it on

Cancers (Basel). 2020 Dec 23;13(1). doi: 10.3390/cancers13010017.

High-Dimensional Analysis of Single-Cell Flow Cytometry Data Predicts Relapse in Childhood Acute Lymphoblastic Leukaemia.

Cancers

Salvador Chulián, Álvaro Martínez-Rubio, Víctor M Pérez-García, María Rosa, Cristina Blázquez Goñi, Juan Francisco Rodríguez Gutiérrez, Lourdes Hermosín-Ramos, Águeda Molinos Quintana, Teresa Caballero-Velázquez, Manuel Ramírez-Orellana, Ana Castillo Robleda, Juan Luis Fernández-Martínez

Affiliations

  1. Department of Mathematics, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  2. Biomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar, 11009 Cádiz, Spain.
  3. Department of Mathematics, Mathematical Oncology Laboratory (MOLAB), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
  4. Instituto de Matemática Aplicada a la Ciencia y la Ingeniería (IMACI), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
  5. ETSI Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
  6. Department of Paediatric Haematology and Oncology, 11407 Hospital de Jerez Cádiz, Spain.
  7. Department of Haematology, Hospital Vírgen del Rocío, 41103 Sevilla, Spain.
  8. Department of Haematology, Hospital Vírgen del Rocío/University of Sevilla, 41103 Sevilla, Spain.
  9. Department of Paediatric Haematology and Oncology, Hospital Infantil Universitario Niño Jesús, Instituto Investigación Sanitaria La Princesa, 28009 Madrid, Spain.
  10. Department of Mathematics, Group of Inverse Problems, Optimisation and Machine Learning, University of Oviedo, 33005 Oviedo, Spain.

PMID: 33374500 PMCID: PMC7793064 DOI: 10.3390/cancers13010017

Abstract

Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse.

Keywords: Acute Lymphoblastic Leukaemia; CD38; Fisher’s Ratio; flow cytometry data; mathematical oncology; personalised medicine; response biomarkers

References

  1. J Clin Oncol. 2012 May 10;30(14):1663-9 - PubMed
  2. Cytometry A. 2019 Sep;95(9):966-975 - PubMed
  3. Hematol Oncol Stem Cell Ther. 2008 Jan-Mar;1(1):34-7 - PubMed
  4. J Biomed Inform. 2011 Aug;44(4):663-76 - PubMed
  5. J Clin Oncol. 2015 Sep 20;33(27):2938-48 - PubMed
  6. Haematologica. 2010 Apr;95(4):679-83 - PubMed
  7. Curr Hematol Malig Rep. 2020 Jun;15(3):203-210 - PubMed
  8. Leuk Res. 2001 Jan;25(1):1-12 - PubMed
  9. Bioinformatics. 2015 Feb 15;31(4):606-7 - PubMed
  10. Bioinformatics. 2019 Oct 15;35(20):4187-4189 - PubMed
  11. Bioinformatics. 2015 May 15;31(10):1623-31 - PubMed
  12. Leuk Lymphoma. 2014 Mar;55(3):611-7 - PubMed
  13. BMC Bioinformatics. 2009 Apr 09;10:106 - PubMed
  14. Blood. 2008 Aug 1;112(3):568-75 - PubMed
  15. J Clin Invest. 2016 Oct 3;126(10):3814-3826 - PubMed
  16. Med Biol Eng Comput. 2020 Nov;58(11):2631-2640 - PubMed
  17. Cytometry A. 2008 Sep;73(9):834-46 - PubMed
  18. Haematologica. 2009 Jul;94(7):1016-9 - PubMed
  19. Blood. 2008 Jun 15;111(12):5477-85 - PubMed
  20. Haematologica. 2019 Apr;104(4):749-755 - PubMed
  21. Physiol Rev. 2008 Jul;88(3):841-86 - PubMed
  22. Leukemia. 2008 Jun;22(6):1207-13 - PubMed
  23. Leukemia. 2017 Mar;31(3):731-734 - PubMed
  24. Leuk Lymphoma. 2013 Nov;54(11):2560-2 - PubMed
  25. Trends Biotechnol. 2013 Jul;31(7):415-25 - PubMed
  26. Br J Haematol. 2018 Jan;180(2):292-296 - PubMed
  27. Leuk Res. 2010 Sep;34(9):1139-42 - PubMed
  28. Life Sci. 2015 Feb 1;122:59-64 - PubMed
  29. Blood. 2010 Apr 22;115(16):3206-14 - PubMed
  30. Nat Med. 2018 May;24(4):474-483 - PubMed
  31. Leuk Res. 2000 Feb;24(2):153-9 - PubMed
  32. Nat Rev Immunol. 2016 Jul;16(7):449-62 - PubMed
  33. Nat Methods. 2013 Mar;10(3):228-38 - PubMed
  34. Blood. 2007 Feb 1;109(3):926-35 - PubMed
  35. Leukemia. 2012 Sep;26(9):1908-75 - PubMed
  36. Blood. 2001 Jun 15;97(12):3925-30 - PubMed
  37. Biomark Res. 2016 Dec 16;4:23 - PubMed
  38. Lancet Haematol. 2020 Jul;7(7):e541-e550 - PubMed
  39. Haematologica. 2019 Mar;104(3):e100-e103 - PubMed
  40. IEEE Trans Pattern Anal Mach Intell. 2010 Mar;32(3):569-75 - PubMed
  41. Leuk Res. 2014 Jan;38(1):42-8 - PubMed
  42. Biomark Res. 2014 Feb 10;2(1):4 - PubMed
  43. Lancet. 2013 Jun 1;381(9881):1943-55 - PubMed
  44. Blood Cancer J. 2017 Jun 30;7(6):e577 - PubMed
  45. Lancet Oncol. 2013 May;14(6):e205-17 - PubMed
  46. Leukemia. 2005 Jun;19(6):1092-4 - PubMed
  47. Cytometry A. 2006 Jun;69(6):541-51 - PubMed
  48. Blood. 2001 Jul 1;98(1):181-6 - PubMed
  49. Int J Lab Hematol. 2011 Feb;33(1):92-6 - PubMed
  50. Semin Hematol. 2001 Apr;38(2):124-38 - PubMed
  51. Sci Rep. 2017 Aug 7;7(1):7402 - PubMed
  52. Cytometry A. 2010 Jul;77(7):705-13 - PubMed

Publication Types

Grant support