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Clinical Chemistry and Laboratory Medicine (CCLM)

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Molecular diagnostics in acute leukemias

Ulrike Bacher1 / Susanne Schnittger2 / Claudia Haferlach2 / Torsten Haferlach2

1Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany

2MLL Munich Leukemia Laboratory GmbH, Munich, Germany

Corresponding author: Prof. Dr. med. Dr. phil. Torsten Haferlach, MD, MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany Phone: +49 89 99017-100, Fax: +49 89 99017-109,

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 47, Issue 11, Pages 1333–1341, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2009.324, October 2009

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Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) both represent highly heterogeneous entities on the basis of diverse cyto- and molecular genetic alterations with considerable influence on prognosis and therapeutic decisions. In recent years, insights into the complex network of molecular markers underlying this diversity have shown marked progress due to the detection of novel mutations, such as nucleophosmin gene (NPM1) in AML, and due to the description of cooperation pathways in leukemogenesis. Also, targeted therapeutic strategies are continuously expanding as illustrated by the tyrosine kinase inhibitor (TKI) imatinib for BCR-ABL positive ALL. Thus, molecular analysis based on various techniques, such as polymerase chain reaction (PCR) has become an essential part of the diagnostic panel for acute leukemia. In addition, cytomorphology, cytogenetics, fluorescence in situ hybridization (FISH), and immunophenotyping with multiparameter flow cytometry (MFC) need to be applied for diagnosis. During the course of disease, the residual leukemic cell load can be monitored by highly sensitive quantitative PCR techniques (“real-time PCR”). At present, new techniques, such as high throughput sequencing (next generation sequencing, NGS) or gene expression profiling with microarrays are being explored for use in hematological malignancies, and are being evaluated in preclinical studies. This demonstrates that molecular diagnostics for acute leukemias are in continuous development. This review summarizes the most important recurrent molecular markers seen in acute leukemias, their role in prognosis and therapy and provides an overview on the relevant PCR techniques.

Clin Chem Lab Med 2009;47:1333–41.

Keywords: acute lymphoblastic leukemia; acute myeloid leukemia; molecular diagnostics; polymerase chain reaction; risk categorization

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