Blast vacuolization in AML patients indicates adverse-risk AML and is associated with impaired survival after intensive induction chemotherapy


Autoři: Olivier Ballo aff001;  Jan Stratmann aff001;  Hubert Serve aff001;  Björn Steffen aff001;  Fabian Finkelmeier aff003;  Christian Brandts aff001
Působiště autorů: Department of Medicine, Hematology/Oncology, Goethe University, Theodor-Stern-Kai, Frankfurt/Main, Germany aff001;  German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany aff002;  Department of Medicine, Gastroenterology, Hepatology and Endocrinology, Goethe University, Theodor-Stern-Kai, Frankfurt/Main, Germany aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223013

Souhrn

Introduction

Vacuolization is a frequently found morphological feature in acute myeloid leukemia (AML) blasts. Subcellular origin and biological function as well as prognostic impact are currently unknown. The aim of this study was to evaluate whether vacuolization correlates with clinically relevant AML features.

Materials & methods

Bone marrow smears of patients diagnosed with AML at the University Hospital Frankfurt between January 2011 and August 2013 were analyzed for blast vacuolization and correlated with clinically relevant AML features. Patients undergoing standard induction chemotherapy were further analyzed for molecular and cytogenetic features as well as treatment response and survival.

Results

14 of 100 patients diagnosed with AML receiving standard induction chemotherapy had evidence of blast vacuolization. Positivity for vacuolization correlated with a CD15 positive immunophenotype and with a higher incidence of high-risk AML according to the European LeukemiaNet risk stratification. AML patients with blast vacuolization had a poor blast clearance after standard induction chemotherapy and poor survival.

Discussion

In conclusion, our findings demonstrate that vacuolization can easily be determined in myeloid leukemia blasts and may be a useful biomarker to predict AML risk groups as well as early treatment response rates and survival.

Klíčová slova:

Bone marrow – Cancer chemotherapy – Deletion mutation – Chemotherapy – Vacuoles – Acute myeloid leukemia – Karyotypes – Cytogenetics


Zdroje

1. Virchow R. Weisses Blut. Froriep´s Notizen. 1845:151–6.

2. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451–8. Epub 1976/08/01. doi: 10.1111/j.1365-2141.1976.tb03563.x 188440.

3. Fenaux P, Le Deley MC, Castaigne S, Archimbaud E, Chomienne C, Link H, et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood. 1993;82(11):3241–9. Epub 1993/12/01. 8241496.

4. Larson RA, Williams SF, Le Beau MM, Bitter MA, Vardiman JW, Rowley JD. Acute myelomonocytic leukemia with abnormal eosinophils and inv(16) or t(16;16) has a favorable prognosis. Blood. 1986;68(6):1242–9. Epub 1986/12/01. 3465376.

5. Gervais C, Murati A, Helias C, Struski S, Eischen A, Lippert E, et al. Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogenetique hematologique. Leukemia. 2008;22(8):1567–75. Epub 2008/06/06. doi: 10.1038/leu.2008.128 18528428.

6. Tang G, DiNardo C, Zhang L, Ravandi F, Khoury JD, Huh YO, et al. MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation. Hum Pathol. 2015;46(1):65–73. Epub 2014/11/13. doi: 10.1016/j.humpath.2014.09.008 25387813.

7. Huang L, Wang SA, DiNardo C, Li S, Hu S, Xu J, et al. Tetraploidy/near-tetraploidy acute myeloid leukemia. Leuk Res. 2017;53:20–7. Epub 2016/12/13. doi: 10.1016/j.leukres.2016.11.016 27951415.

8. Pang CS, Pettenati MJ, Pardee TS. Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia. J Clin Pathol. 2015;68(3):236–40. Epub 2015/01/08. doi: 10.1136/jclinpath-2014-202697 25563333; PubMed Central PMCID: PMC4886850.

9. Hoelzer D, Walewski J, Dohner H, Viardot A, Hiddemann W, Spiekermann K, et al. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014;124(26):3870–9. Epub 2014/11/02. doi: 10.1182/blood-2014-03-563627 25359988; PubMed Central PMCID: PMC4271177.

10. Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C, et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v69–v82. Epub 2016/04/09. doi: 10.1093/annonc/mdw025 27056999.

11. Pappenheim A. Folia Haematologica. 1912:339–45.

12. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, 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):453–74. Epub 2009/11/03. doi: 10.1182/blood-2009-07-235358 19880497.

13. Kern W, Haferlach T, Schoch C, Loffler H, Gassmann W, Heinecke A, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood. 2003;101(1):64–70. Epub 2002/10/24. doi: 10.1182/blood-2002-02-0532 12393605.

14. Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249–59. Epub 2009/09/25. doi: 10.1056/NEJMoa0904544 19776406; PubMed Central PMCID: PMC4480917.

15. Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, Donhuijsen-Ant R, et al. High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood. 1987;69(3):744–9. Epub 1987/03/01. 3469002.

16. Krug U, Buchner T, Berdel WE, Muller-Tidow C. The treatment of elderly patients with acute myeloid leukemia. Dtsch Arztebl Int. 2011;108(51–52):863–70. Epub 2012/01/20. doi: 10.3238/arztebl.2011.0863 22259641; PubMed Central PMCID: PMC3258577.

17. Kerr MA, Stocks SC. The role of CD15-(Le(X))-related carbohydrates in neutrophil adhesion. Histochem J. 1992;24(11):811–26. Epub 1992/11/01. doi: 10.1007/bf01046353 1362195.

18. Campos L, Guyotat D, Archimbaud E, Devaux Y, Treille D, Larese A, et al. Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy. Br J Haematol. 1989;72(2):161–6. Epub 1989/06/01. doi: 10.1111/j.1365-2141.1989.tb07677.x 2757962.

19. Tien HF, Wang CH, Lin MT, Lee FY, Liu MC, Chuang SM, et al. Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan. Cancer Genet Cytogenet. 1995;84(1):60–8. Epub 1995/10/01. doi: 10.1016/0165-4608(95)00084-4 7497445.

20. Dang H, Jiang A, Kamel-Reid S, Brandwein J, Chang H. Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype. Hum Pathol. 2013;44(1):55–61. Epub 2012/09/04. doi: 10.1016/j.humpath.2012.04.008 22939316.

21. Chisini M, Stefanizzi C, Ceglie T, Raponi S, Vozella F, Colafigli G, et al. Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia. Hematol Oncol. 2017;35(4):804–9. Epub 2016/07/13. doi: 10.1002/hon.2331 27400753.

22. Kroschinsky FP, Schakel U, Fischer R, Mohr B, Oelschlaegel U, Repp R, et al. Cup-like acute myeloid leukemia: new disease or artificial phenomenon? Haematologica. 2008;93(2):283–6. Epub 2008/01/29. doi: 10.3324/haematol.11669 18223289.

23. Chen W, Rassidakis GZ, Li J, Routbort M, Jones D, Kantarjian H, et al. High frequency of NPM1 gene mutations in acute myeloid leukemia with prominent nuclear invaginations ("cuplike" nuclei). Blood. 2006;108(5):1783–4. Epub 2006/08/24. doi: 10.1182/blood-2006-03-014340 16926303.

24. Kussick SJ, Stirewalt DL, Yi HS, Sheets KM, Pogosova-Agadjanyan E, Braswell S, et al. A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication. Leukemia. 2004;18(10):1591–8. Epub 2004/09/03. doi: 10.1038/sj.leu.2403458 15343344.

25. Chen YJ, Fang LW, Su WC, Hsu WY, Yang KC, Huang HL. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia. Onco Targets Ther. 2016;9:4453–64. Epub 2016/08/09. doi: 10.2147/OTT.S105664 27499639; PubMed Central PMCID: PMC4959590.


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2019 Číslo 9
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