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Diagnostik akuter Leukämien

Interaktion phänotypischer und genetischer Methoden

Diagnostics of acute leukemias

Interaction of phenotypic and genetic methods

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Zusammenfassung

Die Diagnostik der akuten myeloischen Leukämie (AML) und der akuten lymphatischen Leukämie (ALL) umfasst aufgrund der Heterogenität dieser Entitäten ein breites Methodenspektrum: Zytomorphologie, Histologie, Immunphänotypisierung, klassische Chromosomenanalysen, Fluoreszenz-in-situ-Hybridisierung und Molekulargenetik. Mitunter gibt der zytomorphologische Subtyp bereits Hinweise auf bestimmte genetische Veränderungen oder erlaubt eine Steuerung der weiteren Diagnostik. Die Immunphänotypisierung ermöglicht eine sichere Zuordnung zu einer bestimmten hämatologischen Linie sowie die Charakterisierung des leukämieassoziierten Immunphänotyps als Basis für Verlaufsuntersuchungen. Zytogenetische Veränderungen und molekulare Mutationen sind für die nosologische Zuordnung und das prognostische Profil relevant. Molekulare Marker ermöglichen ferner nach Erreichen einer hämatologischen Remission eine Bestimmung der „minimal residual disease“. Bei hypozellulärer AML oder bei Knochenmarknekrose ist die Histopathologie in Verbindung mit der Immunhistochemie bedeutsam. Hierarchien unter den verschiedenen Techniken ermöglichen einen optimalen Methodenfluss im Labor und eine rasche Diagnosefindung bzw. Klassifikation der Leukämiefälle.

Abstract

Due to the heterogeneity of these disorders, the diagnosis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) requires a broad spectrum of laboratory techniques: cytomorphology, immunophenotyping, chromosome banding analysis, fluorescence in situ hybridization, and molecular genetics. The cytomorphological leukemia subtypes can be indicative for distinct genetic alterations and contribute to the guidance of the further diagnostic process. Immunophenotyping allows to define the hematological lineage and to characterize the leukemia-associated immunophenotype as basis for follow up investigation. Cytogenetic alterations and molecular mutations are essential for the correct classification of cases and for prognostication. Molecular markers are helpful to define the minimal residual disease load after the achievement of hematological complete remission. In cases of hypocellular AML or in case of bone marrow necrosis, histopathology in combination with immunohistochemistry is of importance. Hierarchies between the different techniques catalyze the workflow in the laboratory and allow a rapid diagnosis and classification of the leukemia cases.

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Literatur

  1. Brüggeman M, Schrauder A, Raf T et al (2010) Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia 24:521–535

    Article  Google Scholar 

  2. Choschzick M, Bacher U, Ayuk F, Lebeau A (2010) Immunohistochemistry and molecular analyses in myeloid sarcoma of the breast in a patient with relapse of NPM1-mutated and FLT3-mutated AML after allogeneic stem cell transplantation. J Clin Pathol 63:558–561

    Article  PubMed  CAS  Google Scholar 

  3. Coustan-Smith E, Song G, Clark C et al (2011) New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood 117:6267–6276

    Article  PubMed  CAS  Google Scholar 

  4. Ding L, Ley TJ, Larson DE et al (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481:506–510

    Article  PubMed  CAS  Google Scholar 

  5. Döhner K, Tobis K, Ulrich R (2002) Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16–60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol 20:3254–3261

    Article  PubMed  Google Scholar 

  6. Dufour A, Schneider F, Metzeler KH et al (2010) Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol 28:570–577

    Article  PubMed  CAS  Google Scholar 

  7. Falini B, Mecucci C, Tiacci E et al (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352:254–266

    Article  PubMed  CAS  Google Scholar 

  8. Falini B, Nicoletti I, Martelli MF, Mecucci C (2007) Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc + AML): biologic and clinical features. Blood 109:874–885

    Article  PubMed  CAS  Google Scholar 

  9. Grimwade D, Hills RK, Moorman AV et al (2010) 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 116:354–365

    Article  PubMed  CAS  Google Scholar 

  10. Hoelzer D (2011) Novel antibody-based therapies for acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2011:243–249

    Article  PubMed  Google Scholar 

  11. Kohlman A, Klein HU, Weissman S et al (2011) The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories. Leukemia 25:1840–1848

    Article  Google Scholar 

  12. Luo J, Qi C, Xu W et al (2010) Cytoplasmic expression of nucleophosmin accurately predicts mutation in the nucleophosmin gene in patients with acute myeloid leukemia and normal karyotype. Am J Clin Pathol 133:34–40

    Article  PubMed  CAS  Google Scholar 

  13. Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066

    Article  PubMed  CAS  Google Scholar 

  14. Matutes E, Pickl WF, Van’t Veer M et al (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117:3163–3171

    Article  PubMed  CAS  Google Scholar 

  15. Mufti GJ, Bennet JM, Goasguen J et al (2008) Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 93:1712–1717

    Article  PubMed  Google Scholar 

  16. Paydas S, Ergin M, Baslamisli F et al (2002) Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the literature. Am J Hematol 70:300–305

    Article  PubMed  Google Scholar 

  17. Schnittger S, Schoch C, Dugas M et al (2002) Analysis of FLT3 length mutations in 1,003 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 100:59–66

    Article  PubMed  CAS  Google Scholar 

  18. Schnittger S, Schoch C, Kern W et al (2005) Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 106:3733–3739

    Article  PubMed  CAS  Google Scholar 

  19. Swerdlow S, Campo E, Lee Harris N et al (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon

  20. Taskesen E, Bullinger L, Corbacioglu A et al (2011) Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood 117:2469–2475

    Article  PubMed  CAS  Google Scholar 

  21. Thiede C, Koch S, Creutzig E et al (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107:4011–4020

    Article  PubMed  CAS  Google Scholar 

  22. Trujillo A, McGe C, Cogle CR (2012) Angiogenesis in acute myeloid leukemia and opportunities for novel therapies. J Oncol 2012:128608

    Article  PubMed  Google Scholar 

  23. Walter MJ, Shen D, Ding L et al (2012) Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 366:1090–1098

    Article  PubMed  CAS  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor gibt für sich und seine Koautoren an: CH, WK, SuS, und TH sind Eigentümer der MLL Münchner Leukämie Labor GmbH. UB ist bei der MLL Münchner Leukämie Labor GmbH tätig. MO: Kein Interessenkonflikt.

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Authors and Affiliations

  1. MLL Münchner Leukämie Labor GmbH, Max-Lebsche-Platz 31, 81377, München, Deutschland

    U. Bacher, C. Haferlach, S. Schnittger, W. Kern &  T. Haferlach

  2. Institut für Pathologie, Caritas-Krankenhaus, Bad Mergentheim, Deutschland

    M.M. Ott

Authors
  1. U. Bacher
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  2. C. Haferlach
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  3. S. Schnittger
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  4. W. Kern
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  5. M.M. Ott
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  6. T. Haferlach
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Correspondence to T. Haferlach.

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Bacher, U., Haferlach, C., Schnittger, S. et al. Diagnostik akuter Leukämien. Pathologe 33, 528–538 (2012). https://doi.org/10.1007/s00292-012-1653-1

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  • DOI: https://doi.org/10.1007/s00292-012-1653-1

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