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Bacher U.,The Interdisciplinary Center | Schnittger S.,MLL Munich Leukemia Laboratory GmbH | Haferlach T.,MLL Munich Leukemia Laboratory GmbH
Current Opinion in Oncology | Year: 2010

Purpose of review: Acute myeloid leukemia (AML) is a highly heterogeneous disorder being composed of various genetically defined subtypes. In recent years, molecular research provided the basis for a more differentiated characterization of AML patients, for example, of the large subgroup with normal karyotypes. This review summarizes the current status of molecular diagnostics in AML and refers to the diagnostic techniques being most suitable for the individual markers. Recent findings: A molecular data set based on mutations of the NPM1, FLT3, and CEBPA genes and the MLL-PTD provides a prognostically relevant risk stratification that can support the decision pro or con an allogeneic hematopoietic stem cell transplantation in first remission. The panel of known molecular markers is continuously increasing, for example, considering the recently described TET2 and IDH1 mutations. The introduction of next generation sequencing will certainly catalyze the molecular characterization of AML. Monitoring of the minimal residual disease load with quantitative real-time PCR can be performed for NPM1 and MLL-PTD-mutated cases. Summary: Targeted therapy studies with FLT3 inhibitors for patients with FLT3-mutated AML as single agents or combined with chemotherapy illustrate the translation of the molecular techniques into clinical practice already being realized in distinct subgroups of AML. © 2010 Wolters Kluwer Health | Lippincott Williams and Wilkins. Source


Schnittger S.,MLL Munich Leukemia Laboratory GmbH | Bacher U.,University of Hamburg | Dicker F.,MLL Munich Leukemia Laboratory GmbH | Kern W.,MLL Munich Leukemia Laboratory GmbH | And 3 more authors.
Genes Chromosomes and Cancer | Year: 2010

In patients with chronic myeloid leukemia (CML), resistance against imatinib is associated with mutations in the kinase domain (KD) of the BCR-ABL1 fusion gene and/or with additional chromosomal abnormalities (ACAs) secondary to the Philadelphia chromosome. To evaluate associations between these molecular and cytogenetic events, we correlated cytogenetic data with results of KD mutation analysis in 205 CML patients with acquired resistance to imatinib (100 females, 105 males, 17.9-90.3 years). In 79/205 patients (38.5%), at least one KD mutation was detected; in 13/79 (16.5%) even two different mutations were observed. A second KD mutation was frequent in cases with G250E (4/9), E255V (1/3), T315I (5/18), F317L (2/7), F359C/V (4/7), or H396R (2/3), but was never detected in cases with V299L (n = 3) or Y253H (n = 4). With respect to cytogenetics, ACAs were identified in 76/205 patients (37.1%), in 29 (36.7%) together with KD mutations. ACAs were frequent in cases with E255V (2/3), T315I (8/18), F317L (4/7), F359C/V (4/7), or H396R (2/3), but rare in those with M351T (1/9). Therefore, some KD mutations (e.g., T315I) might be associated with higher genetic instability paving the way to additional cytogenetic and molecular genetic events. © 2010 Wiley-Liss, Inc. Source


Patterer V.,MLL Munich Leukemia Laboratory GmbH | Schnittger S.,MLL Munich Leukemia Laboratory GmbH | Kern W.,MLL Munich Leukemia Laboratory GmbH | Haferlach T.,MLL Munich Leukemia Laboratory GmbH | Haferlach C.,MLL Munich Leukemia Laboratory GmbH
Annals of Hematology | Year: 2013

The translocation t(8;9)(p22;p24) is a rare event that results in the fusion of JAK2 to PCM1 and thus leads to the activation of the Janus Kinase 2. In 2008, the WHO introduced a new entity called "Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1", which are characterized by the formation of a fusion gene encoding an aberrant tyrosine kinase. These disorders share characteristics with myeloproliferative neoplasms and typically show an eosinophilia. We here now report on 6 new cases with PCM1-JAK2 fusion. These patients show characteristics with respect to epidemiology, clinical presentation, and genetic changes that are very similar to patients with rearrangements of PDGFRA, PDGFRB, or FGFR1. Our data suggests the integration of cases with JAK2-PCM1 fusion in the respective WHO category of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. © 2013 Springer-Verlag Berlin Heidelberg. Source

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