Immunophenotypic investigation of infant acute myeloid leukemia
https://doi.org/10.17650/1818-8346-2013-8-1-33-39
Abstract
Aim of the study – characterization of immunophenotype in infant acute myeloid leukemia (AML). 90 patients (40 boys and 50 girls) with acute leukemia (AL) aged up to 365 days were included in the current study. AML was found more frequently in infants than in older children (26.67 % and 10.83 % respectively; p = 0.0002). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD99, CD61, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD61-negativity, high CD99, CD15, CD133 and NG2 expression were immunophenotypic signatures of MLLrearranged infant AML, although CD99 and NG2 had the highest diagnostic efficacy. Thus infants’ AML immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ AML allows predicting presence of MLL rearrangements by either CD99 or NG2 expression.
About the Authors
A. M. Popov
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
G. A. Tsaur
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
T. Yu. Verzhbitskaya
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
O. V. Streneva
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
E. V. Shorikov
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
L. I. Saveliev
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Ural State Medical Academy
Russian Federation
Russian Federation
L. G. Fechina
Regional Childrenʼs Clinical Hospital №1
Research Institute of Medical Cell Technologies
Russian Federation
Russian Federation
References
1. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Swerdlow S., Campo E., Harris N.L. et al. (eds.). Lyon, France: IARC, 2008.
2. Vardiman J., Thiele J., Arber D. et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;111:937–51.
3. Ross J., Davies S., Potter J., Robison L 1994;16:243–72.
4. Pui C.-H., Kane J., Crist W. Biology and treatment of infant leukemias. Leukemia 1995;9:762–9.
5. Biondi A., Cimino G., Pieters R., Pui C.H. Biological and therapeutic aspects of infant leukemia. Blood 2000;96:24–33.
6. Webb D., Harrison C., Stevens R. et al. Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood 2001;98:1714–20.
7. Pui C.-H., Kalwinsky D., Schell M. et al. Acute nonlymphoblastic leukemia in infants: clinical presentation and outcome. J Clin Oncol 1988;6:1008–13.
8. Chessells J., Harrison C., Kempski H. et al. Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party. Leukemia 2002;16:776–84.
9. van Wering E., Kamps W. Acute leukemia in infants. A unique pattern of acute nonlymphocytic leukemia. Am J Pediatr Hematol Oncol 1986;8:220–4.
10. Vormoor J., Ritter J., Creutzig U. et al. Acute myelogenous leukaemia in children under 2 years – experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group. Br J Cancer 1992;18(Suppl.):63–7.
11. Pui C-H., Raimondi S., Srivastava D. et al. Prognostic factors in infants with acute myeloid leukemia. Leukemia 2000;14:684–7.
12. Sorensen P., Chen C., Smith F. et al. Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes. J Clin Invest 1994;93:429–37.
13. Park K., Lee D., Lee H. et al. Granulocytic sarcoma in MLL-positive infant acute myelogenous leukemia: fluorescence in situ hybridization study of childhood acute myelogenous leukemia for detecting MLL rearrangement. Am J Pathol 2001;159(6):2011–6.
14. Pieters R. Biology and treatment of infant leukemias. In: Pui С.-H. (editor), Treatment of Acute Leukemias: New Directions for Clinical Research. Totowa, USA: Humana Press, 2003. Pp. 61–73.
15. Felix C., Lange B. Leukemia in infants. Oncologist 1999;4:225–40.
16. Balgobind B., Raimondi S., Harbott J. et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489–96.
17. Harrison C., Hills R., Moorman A. et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 2010;28(16):2674–81.
18. Neuhoff von C., Reinhardt D., Sander A. et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol 2010;28(16):2682–9.
19. Chantrain C.F., Poirel H.A. The genetic signature of acute leukemia in infancy. Hem Oncol 2010;1:1–8.
20. Meyer С., Kowarz E., Hofmann J. et al. New insights to the MLL recombinome of acute leukemias. Leukemia 2009;23:1490–9.
21. Armstrong S.A., Staunton J.E., Silverman L.B. et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genetics 2002;30:41–7.
22. Zangrando A., Dell’Orto M.C., te Kronnie G., Basso G. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage-specific signatures. BMC Med Genom 2009;23:2–36.
23. Stam R.W., Schneider P., Hagelstein J.A.P. et al. Gene expression profiling-based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants. Blood 2010;115:2835–44.
24. Qazi S., Uckun F.M. Gene expression profiles of infant acute lymphoblastic leukemia and its prognostically distinct subsets. Br J Hematol 2010;149:865–73.
25. Szczepanski T., Harrison C.J., van Dongen J.J.M. Genetic aberrations in paediatric acute leukaemias and implication for management of patients. Lancet Oncol 2010;11:880–9.
26. Borkhardt A., Vuchter C., Viehmann S. et al. Infant acute lymphoblastic leukemia – combined cytogenetic, immunophenotypical and molecular analysis of 77 cases. Leukemia 2002;16:1685–90.
27. Hrusak O., Porwit-MacDonald A. Antigen expression patterns reflecting genotype of acute eukemias. Leukemia 2002;16:1233–58.
28. De Zen L., Bicciato S., te Kronnie G., Basso G. Computational analysis of flow cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification. Leukemia 2003;17:1557–65.
29. Schwartz S., Reider H., Schlager B. et al. Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangements and a CD10–/CD24–/CD65s+/CD15+ B-cell immunophenotype. Leukemia 2003;17:1589–95.
30. Attarbaschi A., Mann G., Konig M. et al. Mixed Lineage Leukemia – rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity. Clin Cancer Res 2006;15(10):2988–94.
31. Попов А.М., Цаур Г.А., Вержбицкая Т.Ю. др. Иммунофенотипическая характеристика острого лимфобластного лейкоза у детей первого года жизни. Онкогематол 2012;2:16–23.
32. Smith F.O., Rauch C., Williams D.E. et al. The human homologue of rat NG2, a chondroitin sulphate chromosome band 11q23blasts from poor-prognosis patients with abnormalities of hematopoietic cells but is expressed by acute myeloid leukemia proteoglycan, is not expressed on the cell surface of normal. Blood 1996;87:1123–33.
33. Mauvieux L., Delabesse E., Bourquelot P. et al. NG2 expression in MLL rearranged acute myeloid leukaemia is restricted to monoblastic cases. Br J Haematol 1999;107:674–6.
34. Wuchter C., Harbott J., Schoch C. et al. Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody 7.1. Leukemia 2000;14:1232–8.
35. Bene M., Castoldi G., Knapp W. et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9(10):1783–6.
36. ISCN 2009: An International System Human Cytogenetic Nomenclature (2009). Eds.: Shaffer L.G., Slovak M., Campbell L. Karger, Basel, Switzerland, 2009.
37. Borkhardt A., Repp R., Haupt E. et al. Molecular analysis of MLL/AF4 recombination in infant acute lymphoblastic leukemia. Leukemia 1994;8:549–53.
38. Pallisgaard N., Hokland P., Riishoj D. et al. Multiplex reverse transcriptionpolymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia.
39. Blood 1998;92:574–88.
40. Цаур Г.А., Наседкина Т.В., Попов А.М. и др. Время достижения молекулярной ремиссии как фактор прогноза у детей первого года жизни с острым лимфобластным лейкозом. Онкогематол 2010;2:46–54.
41. Weinstein S., Obuchowski N.A., Lieber M.L. Clinical evaluation of diagnostic tests. Am J Roentgenol 2005;184:14–9.
42. Bernstein J., Dastugue N., Haas O. et al. Nineteen cases of the t(1;22)(p13;q13) acute megakaryoblastic leukaemia of infants/children and a review of 39 cases: report from a t(1;22) study group. Leukemia 2000;14:216–8.
43. Матвеева Е.А., Казакова А.Н., Калинина И.И. и др. Методы молекулярной цитогенетики для диагностики острого мегакариобластного лейкоза. Онкогематол 2012;2:51–6.
44. Hilden J., Smith F., Frestedt J. et al. MLL Gene Rearrangement, Cytogenetic 11q23 Abnormalities, and Expression of the NG2 Molecule in Infant Acute Myeloid Leukemia. Blood 1997;89(10):3801–5.
45. Kawasaki H., Isoyama K., Eguchi M. et al. Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group. Blood 2001;98(13):3589–90.
46. Rubnitz J., Raimondi S., Tong X. et al. Favorable Impact of the t(9;11) in Childhood Acute Myeloid Leukemia. J Clin Oncol 2002;20:2302–9.
47. Balgobind B., Zwaan C., Pieters R., van den Heuvel-Eibrink M. The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia. Leukemia 2011;25:1237–48.
48. Thirman M., Gill H., Burnett R. et al. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. New Eng J Med 1993;329:909–14.
49. Cuthbert G., Thompson K., Breese G. et al. Sensitivity of FISH in detection of MLL translocations. Genes Chromosomes Cancer 2000;29:180–5.
50. von Bergh A., Emanuel B., Zelderen-Bhola van S. et al. A DNA probe combinationfor improved detection of MLL/11q23 breakpoints by double-color interphase- FISH in acute leukemias. Genes Chromosomes Cancer 2000;28:14–22.
51. Dyson M., Talley P., Reilly J. et al. Detection of cryptic MLL insertions using a commercial dual-color fluorescence in situ hybridization probe. Cancer Genet Cytogenet 2003;147:81–3.
52. Цаур Г.А., Плеханова О.М., Гиндина Т.Л. и др. Применение метода флуоресцентной гибридизации in situ для выявления перестроек гена MLL при острых лейкозах у детей первого года жизни. Мед ген 2012;7:35–43.
Review
For citations:
Popov A.M., Tsaur G.A., Verzhbitskaya T.Yu., Streneva O.V., Shorikov E.V., Saveliev L.I., Fechina L.G. Immunophenotypic investigation of infant acute myeloid leukemia. Oncohematology. 2013;8(1):33-39. (In Russ.) https://doi.org/10.17650/1818-8346-2013-8-1-33-39
Views:
9978
Email this article 