Issue Highlights – Cytometry Part B November 2013 Pediatric oncology remains a particularly brutal dark zone of human experience in the 21st century, especially to those of us who are dedicated to work with sick children. Just when we remind ourselves about the unrelenting cruelty of reality, we hear of modest but encouraging breakthrough-steps signaling progress in efforts to mitigate pediatric cancer. In a book called Gay Science, Friedrich Nietzsche was dealing with eternal recurrences, which is often misinterpreted as a metaphoric description of mind over matter. However, some believe that Nietzsche’s interpretation had to do with the concepts related to the story of Zarathustra as it is described also by Nietzsche: "I teach you the Uberman. Man is something that shall be overcome. What have you done to overcome him?”(1,2). Ironically cells programmed for eternal survival are the ones stealing life from youth fighting lymphomas and leukemia. Here are three articles that reflect how mankind is making some modest progress on the way to “Uberman” status.
Some Current Progress in Pediatric Diagnostics: Gaipa et al. in their review of detection of minimal residual disease conclude that risk assessment will achieve further refinement by combining implementation of minimal residual disease (MRD) and PCR defined lesions associated with acute lymphoblastic leukemia (ALL) in children (3). This review is a decisive illustration of a situation where immunophenotyping and molecular biology together are forming a formidable and powerful diagnostic tool. However, the road to improved diagnostics is paved with significant number of obstacles (4-10). According to Boztug et al., the addition of CD 11a as an immunophenotyping marker to the currently accepted flow cytometry panel does reinforce diagnosis of acute megakaryoblastic leukemia (AML), classical Down syndrome (DS) -AML and works for transient myeloproliferative disease (TMD) (11). They claim that CD11a deficiency is a strong supportive indicator of the above three conditions in children. Understanding of the role of genetic dysfunctions is critical to unravel the path to eliminate malignancies (12-14). Sharawat et al. demonstrated that combined co-expression of CD135 and CD117 as immunophenotyping markers serve as independent predictors of poor outcome in pediatric acute myeloid leukemia (AML) (15). This study is yet another demonstration that the late 20th century biomedical platform, flow cytometry, continues to make significant contributions in resolving some of the elements of disease outcomes in pediatric oncology in the second decade of the 21st century. F. Mandy International Centre for Infectious Diseases, Ottawa, ON Canada E-mail: [email protected] This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/cytob.21136
Literature Cited 1. Hollingdale RJ. Nietzche: The Man and his Philosophy, p. 21. Cambridge University Press, 1999. 2. Nietzsche, Friedrich (2006). Nietzsche: Thus Spoke Zarathustra. Adrian Del Caro and Robert Pippin, editors. Cambridge: Cambridge University Press. 3. Gaipa G, Basso G, Biondi A, Campana D. Detection of Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia. Cytometry B Clin Cytom 2013; 84B: cyto.b.21101. 4. Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, Karawajew L, Benetello A, P.tschger U, Husak Z, Gadner H, Biondi A, Ludwig WD, Basso G. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom. 2008;74B:331-340. 5. Preffer F, Dombkowski D. Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom. 2009;76B:295-314. 6. Kamnesh RP, Mund JA, Johnson C, Vik TA, Ingram DA, and Case J. Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom. 2011;80B:335-338. 7. DiGiuseppe JA, Cardinali J. Improved compensation of the fluorochrome AmCyan usingcellular controls. Cytometry B Clin Cytom. 2011;80B:191-194. 8. DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry B Clin Cytom. 2009;76B:150-155. 9. Borowitz MJ, Pullen DJ, Winick N, Martin PL, Bowman WP, Camitta B. Comparison of diagnostic and relapse flow cytometry phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a report from the children's oncology group. Cytometry B Clin Cytom. 2005;68B:1824. 10. Dworzak MN, Gaipa G, Schumich A, Maglia O, Ratei R, Veltroni M, Husak Z, Basso G,Karawajew L, Gadner H, Biondi A. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the
AIEOP-BFM-ALL-FLOW-MRD-Study Group. Cytometry B Clin Cytom. 2010;78B:147-153. 11. Boztug H, Schumich A, Poetschger U, Muehlegger N, Kolenova A, Reinhardt K, Dworzak M. Blast cell deficiency of CD11a as a marker of acute megakaryoblastic leukemia and transient myeloproliferative disease in children with and without Down syndrome. Cytometry B Clin Cytom 2013; 84B: cyto.b.21082. 12. Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, Karawajew L, Benetello A, Potschger U, Husak Z and others. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom 2008;74B:331-340. 13. Hoffmann MH, Klausen TW, Boegsted M, Larsen SF, Schmitz A, Leinoe EB, Schmiegelow K, Hasle H, Bergmann OJ, Sorensen S, et al. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia. Cytometry B Clin Cytom 2012;82B:123-131. 14. Merzianu M, Wallace PK. Case study interpretation–Portland: Case 4. Acute leukemia of ambiguous lineage, unclassifiable. Cytometry B Clin Cytom 2012;82B:186-191. 15. Sharawat S, Gupta R, Raina V, Kumar L, Sharma A, Iqbal S, Bakhsi R, Vishnubhatla S. Increased Co-Expression of c-KIT and FLT-3 Receptors on Myeloblasts: Independent Predictor of Poor Outcome in Pediatric Acute Myeloid Leukemia. Cytometry B Clin Cytom. 2013; 84B: cyto.b.21098.
Some Current Progress in Pediatric Diagnostics: Gaipa et al. in their review of detection of minimal residual disease conclude that risk assessment will achieve further refinement by combining implementation of minimal residual disease (MRD) and PCR defined lesions associated with acute lymphoblastic leukemia (ALL) in children (3). This review is a decisive illustration of a situation where immunophenotyping and molecular biology together are forming a formidable and powerful diagnostic tool. However, the road to improved diagnostics is paved with significant number of obstacles (4-10). According to Boztug et al., the addition of CD 11a as an immunophenotyping marker to the currently accepted flow cytometry panel does reinforce diagnosis of acute megakaryoblastic leukemia (AML), classical Down syndrome (DS) -AML and works for transient myeloproliferative disease (TMD) (11). They claim that CD11a deficiency is a strong supportive indicator of the above three conditions in children. Understanding of the role of genetic dysfunctions is critical to unravel the path to eliminate malignancies (12-14). Sharawat et al. demonstrated that combined co-expression of CD135 and CD117 as immunophenotyping markers serve as independent predictors of poor outcome in pediatric acute myeloid leukemia (AML) (15). This study is yet another demonstration that the late 20th century biomedical platform, flow cytometry, continues to make significant contributions in resolving some of the elements of disease outcomes in pediatric oncology in the second decade of the 21st century. F. Mandy International Centre for Infectious Diseases, Ottawa, ON Canada E-mail: [email protected] This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/cytob.21136
Literature Cited 1. Hollingdale RJ. Nietzche: The Man and his Philosophy, p. 21. Cambridge University Press, 1999. 2. Nietzsche, Friedrich (2006). Nietzsche: Thus Spoke Zarathustra. Adrian Del Caro and Robert Pippin, editors. Cambridge: Cambridge University Press. 3. Gaipa G, Basso G, Biondi A, Campana D. Detection of Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia. Cytometry B Clin Cytom 2013; 84B: cyto.b.21101. 4. Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, Karawajew L, Benetello A, P.tschger U, Husak Z, Gadner H, Biondi A, Ludwig WD, Basso G. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom. 2008;74B:331-340. 5. Preffer F, Dombkowski D. Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom. 2009;76B:295-314. 6. Kamnesh RP, Mund JA, Johnson C, Vik TA, Ingram DA, and Case J. Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom. 2011;80B:335-338. 7. DiGiuseppe JA, Cardinali J. Improved compensation of the fluorochrome AmCyan usingcellular controls. Cytometry B Clin Cytom. 2011;80B:191-194. 8. DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry B Clin Cytom. 2009;76B:150-155. 9. Borowitz MJ, Pullen DJ, Winick N, Martin PL, Bowman WP, Camitta B. Comparison of diagnostic and relapse flow cytometry phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a report from the children's oncology group. Cytometry B Clin Cytom. 2005;68B:1824. 10. Dworzak MN, Gaipa G, Schumich A, Maglia O, Ratei R, Veltroni M, Husak Z, Basso G,Karawajew L, Gadner H, Biondi A. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the
AIEOP-BFM-ALL-FLOW-MRD-Study Group. Cytometry B Clin Cytom. 2010;78B:147-153. 11. Boztug H, Schumich A, Poetschger U, Muehlegger N, Kolenova A, Reinhardt K, Dworzak M. Blast cell deficiency of CD11a as a marker of acute megakaryoblastic leukemia and transient myeloproliferative disease in children with and without Down syndrome. Cytometry B Clin Cytom 2013; 84B: cyto.b.21082. 12. Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, Karawajew L, Benetello A, Potschger U, Husak Z and others. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible. Cytometry B Clin Cytom 2008;74B:331-340. 13. Hoffmann MH, Klausen TW, Boegsted M, Larsen SF, Schmitz A, Leinoe EB, Schmiegelow K, Hasle H, Bergmann OJ, Sorensen S, et al. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia. Cytometry B Clin Cytom 2012;82B:123-131. 14. Merzianu M, Wallace PK. Case study interpretation–Portland: Case 4. Acute leukemia of ambiguous lineage, unclassifiable. Cytometry B Clin Cytom 2012;82B:186-191. 15. Sharawat S, Gupta R, Raina V, Kumar L, Sharma A, Iqbal S, Bakhsi R, Vishnubhatla S. Increased Co-Expression of c-KIT and FLT-3 Receptors on Myeloblasts: Independent Predictor of Poor Outcome in Pediatric Acute Myeloid Leukemia. Cytometry B Clin Cytom. 2013; 84B: cyto.b.21098.
