The specific features of the immunophenotype of blast cells in patients with de novo normal karyotype acute myeloid leukemia and FLT3-ITD mutation


Cite item

Full Text

Abstract

AIM: To study the specific features of de novo acute myeloid leukemia (AML) with FLT3-ITD mutation/MATERIAL AND METHODS: The results of examination were analyzed in 101 patients. Bone marrow morphological specimens were stained with Pappenheim stain. The karyotype was investigated using the standard GTG-banding method. Blast cells were immunotyped in a five-color analysis on a Cytomics FC 500 laser flow cytofluorometer/RESULTS: FLT3-ITD mutation was identified in 21 patients who had a varying morphological nature of blasts, different karyotype variants, and frequently additional NPM1 gene mutation. The distinctive property of 10 patients with normal karyotype and FLT3-ITD mutation (without NPM1 gene mutation) was the larger number of cases with high expression of HLA-DR and CD7 than in the control group that included 18 patients with normal karyotype AML without FLT3-ITD nutation: 50% versus 6.2% (p=0.007) and 100% versus 55.6% (p=0.014), respectively/CONCLUSION: Normal karyotype AML with FLT3-ITD mutation is a group that is homogeneous in the biological phenotype of leukemia cells.

Full Text

Особенности иммунофенотипа бластных клеток у больных de novo острым миелоидным лейкозом с нормальным кариотипом и мутацией FLT3-ITD. - Резюме. Цель исследования. Изучение особенностей de novo острого миелоидного лейкоза (ОМЛ) с мутацией FLT3-ITD. Материалы и методы. Проведен анализ результатов обследования 101 больного. Морфологические препараты костного мозга окрашивали по Паппенгейму. Кариотип изучали с помощью стандартного GTG-метода. Иммунофенотипирование бластных клеток проводили в пятицветном анализе на лазерном проточном цитофлуориметре Cytomics FC 500. Результаты. Мутация FLT3-ITD обнаружена у 21 больного, которые имели разную морфологическую природу бластов, разные варианты кариотипа и нередко дополнительную мутацию гена NPM1. Отличительной особенностью у 10 больных с нормальным кариотипом и мутацией FLT3-ITD (без мутации гена NPM1) было увеличение числа случаев с высокой экспрессией HLA-DR и CD7 по сравнению с контрольной группой, в которую включены 18 больных ОМЛ с нормальным кариотипом и без мутации FLT3-ITD: 50% против 6,2% (р=0,007) и 100% против 55,6% (р=0,014) соответственно. Заключение. ОМЛ с нормальным кариотипом и мутацией FLT3-ITD представляет группу, однородную по биологическому фенотипу лейкозных клеток.
×

References

  1. Волкова М.А. Клиническая онкогематология. М: Медицина 2007; 1120.
  2. Estey E., Dohner H. Acute myeloid leukaemia. Lancet 2006; 368 (9550): 1894-1907.
  3. Vardiman J.W., Harris N.L., Brunning R.D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100 (7): 2292-2302.
  4. Vardiman J.W., Thiele J., Arber D.A. et al. The 2008 revision of the World Health Organisation (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2008; 114 (5): 937-951.
  5. Грицаев С.В., Мартынкевич И.С., Абдулкадыров К.М. и др. Острый миелобластный лейкоз с транслокацией t(8;21)(q22;q22): ретроспективный анализ выживаемости больных. Вестн гематол 2010; 1: 80-85.
  6. Sanderson R.N., Johnson P.R.E., Moorman A.V. et al. Population-based demographic study of karyotypes in 1709 patients with adult acute myeloid leukemia. Leukemia 2006; 20 (3): 444-450.
  7. Grimwade D., Hills R.K., Moorman A.V. et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116 (3): 354-365.
  8. Dohner H., Estey E.H., Amadori S. et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115 (3): 453-474.
  9. Estey E.H. Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 2012; 87 (1): 90-99.
  10. Rau R., Brown P. Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukemia: towards definition of a new leukemia entity. Hematol Oncol 2009; 27 (4): 171-181.
  11. Haferlach C., Mecucci C., Schnittger S. et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 2009; 114 (14): 3024-3032.
  12. Falini B., Martelli M.P., Bolli N. et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 2011; 117 (4): 1109-1120.
  13. Мартынкевич И.С., Грицаев С.В., Москаленко М.В. и др. Мутации генов FLT3 и NPM1 у больных острыми миелоидными лейкозами и влияние мутации FLT3-ITD на выживаемость больных с нормальным кариотипом. Тер арх 2010; 12: 33-39.
  14. Breems D.A., Löwenberg B. Acute myeloid leukemia with monosomal karyotype at the far end of the unfavorable prognostic spectrum. Haematologica 2011; 96 (4): 491-493
  15. Грицаев С.В., Мартынкевич И.С., Мартыненко Л.С. и др. Возраст и кариотип - факторы риска у больных первичным острым миелоидным лейкозом. Клин онкогематол 2010; 4: 359-364.
  16. Grimwade D., Mrózek K. Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia. Hematol Oncol Clin North Am 2011; 25 (6): 1135-1161.
  17. Грицаев С.В., Мартынкевич И.С., Петрова Е.В. и др. Выживаемость больных CBF-вариантами de novo острого миелоидного лейкоза (ОМЛ) и кариотип. Вестн гематол 2012; 4: 11.
  18. Deeg H.J., Scott B.L., Fang M. et al. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood 2012; 120 (7): 1398-1408.
  19. Cornelissen J.J., Breems D., van Putten W.L. et al. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol 2012; 30 (17): 2140-2146.
  20. Elliott M.A., Litzow M.R., Letendre L.L. et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood 2007; 110 (13): 4172-4174.
  21. Lancet J.E., List A.F., Bello C.M. et al. Outcomes and prognostic factors following double-induction chemotherapy in AML - a large, single institutional experience. Blood 2011; 118 (21): Abstr. 3605.
  22. Gilliland D.G., Griffin J.D. Role of Flt3 in leukemia. Curr Opin Hematol 2002; 9 (4): 274-281.
  23. Rombouts W.J., Blokland I., Lowenbery B. et al. Biologic characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplication in the Flt3 gene. Leukemia 2000; 14 (4): 675-683.
  24. Kottaridis P.D., Gale R.E., Frew M.E. et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 Trials. Blood 2001; 98 (6): 1752-1759.
  25. Schnittger S., Schoch C., Dugas M. et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002; 100 (1): 59-66.
  26. Kayser S., Schlenk R.F., Krauter J. et al. Prognostic impact of mutant to wild-type ratio and insertion site in acute myeloid leukemia with FLT3 internal tandem duplication. Blood 2012; 120 (21): Abstr. 785.
  27. Gale R.E., Green C., Allen C. et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008; 111 (5): 2776-2784.
  28. Breccia M., Frustaci A.M., Cannella L. et al. Comorbidities and FLT3-ITD abnormalities as independent prognostic indicators of survival in elderly acute myeloid leukaemia patients. Hematol Oncol 2009; 27 (3): 148-153.
  29. de Jonge H.J.M., Valk P.J.M., S.J.M. de Bont E.S.J.M. et al. Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD. Haematologica 2011; 96 (9): 1310-1317.
  30. Noguera N.I., Breccia M., Divona M. et al. Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia 2002; 16 (11): 2185-2189.
  31. Callens C., Chevret S., Cayuela J.-M. et al. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group. Leukemia 2005; 19 (7): 1153-1160.
  32. Barragan E., Montesinos P., Camos M. et al. Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy. Haematologica 2011; 96 (10): 1470-1477.
  33. Frohling S., Schlenk R.F., Breitruck J. et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 2002; 100 (13): 4372-4380.
  34. Chauhan P.S., Bhushan B., Mishra A.K. et al. Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features. Med Oncol 2011; 28 (2): 544-551.
  35. Ostronoff А., Othus M., Kantarjian H.M. et al. A scoring system for prediction of FLT3-ITD positivity in patients with newly diagnosed acute myeloid leukemia. Blood 2012; 120 (21): Abstr. 2590.
  36. Chandía M.A., Vidriales M.B., Chillón C. et al. Immunophenotypic characteristics of CD34+ cells according to genetic markers in acute myeloid leukemias with normal karyotype. Blood 2012; 120 (21): Abstr. 2554.
  37. Rausei-Mills V., Chang, M.D., Gaal K.K. et al. Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute myeloid leukemias with FLT3/ITD mutation. Am J Clin Pathol 2008; 129 (4): 624-629.
  38. Schneider F., Hoster E., Schneider S. et al. Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML). Ann Hematol 2012; 91 (1): 9-18.
  39. Stone R.M., Fischer T., Paquette R. et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012; 26 (9): 2061-2068.
  40. Rollig C., Brandts C., Shaid S. et al. Survey and analysis of the efficacy and prescription pattern of sorafenib in patients with acute myeloid leukemia. Leuk Lymphoma 2012; 53 (6): 1062-1067.
  41. Pallis M., Turzanski J., Grundy M. et al. Resistance to spontaneous apoptosis in acute myeloid leukaemia blasts is associated with p-glycoprotein expression and function, but not with the presence of FLT3 internal tandem duplications. Br J Haemat 2003; 120 (6): 1009-1016.
  42. Marzac C., Teyssandier I., Calendini O. et al. Flt3 internal tandem duplication and P-glycoprotein functionality in171 patients with acute myeloid leukemia. Clin Cancer Res 2006; 12 (23): 7018-7024.
  43. Galimberti S., Rossi A., Palumbo G.A. et al. FLT3 mutations do not influence MDR-1 gene expression in acute myeloid leukemia. Anticancer Res 2003; 23 (4): 3419-3426.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2014 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies