Article: Patient-specific analysis of FLT3 internal tandem duplications for the prognostication and monitoring of acute myeloid leukemia.[show abstract] [hide abstract]
ABSTRACT: Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 ( FLT3) gene occur in 13-35% of patients with acute myeloid leukemia (AML). FLT3-ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo-SCT). To investigate FLT3-ITD length, position, and mutational load in AML cases, we developed patient-specific quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays and correlated the results with established sensitive minimal residual disease (MRD) parameters and clinical outcome. In 409 patients with AML, FLT3-ITDs could be detected in 54 cases (13%). Within our cohort, patients with FLT3-ITD ≥ 45 base pairs had significantly higher relapse rates (P = 0.03) and a worse overall survival (P = 0.03). Our method could be applied to 97% of FLT3-ITD-positive patients and was as sensitive as other MRD parameters such as PML-RARA , NPM1 mutations, or MLL -PTD (correlation: r = 0.63; 0.99, and 0.99, respectively). MRD negativity predicted lasting remission independent of allo-SCT (N = 7) or non-allo-SCT (N = 9). All paired diagnostic/relapsed samples showed FLT3-ITD positivity. Compared with bone marrow samples, FLT3-ITD analyses appeared to be equivalently sensitive in peripheral blood. We conclude that individualized monitoring of FLT3-ITD in patients with AML may guide treatment decisions and should be evaluated for the indication for allo-SCT.European Journal Of Haematology 03/2012; 89(1):53-62. · 2.61 Impact Factor
Article: A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasia resulting in a fusion of IGL and CCND1: case report.[show abstract] [hide abstract]
ABSTRACT: The chromosomal translocation (11;14)(q13;q32) rearranging the locus for cyclin D1 (CCND1) to that of the immunoglobulin heavy chain (IGH) can be found in virtually all cases of mantle cell lymphoma (MCL), while other CCND1 translocations are extremely rare. As CCND1 overexpression and activation is a hallmark of MCL it is regarded as a central biological mechanism in the development and maintenance of this disease.Here we present a patient initially diagnosed with chronic lymphocytic leukemia (CLL) where chromosome banding analysis revealed, among other aberrations, a translocation (11;22)(q13;q11.2). We show by fluorescence in situ hybridization (FISH) analysis that on chromosome 22 the immunoglobulin light chain lambda (IGL) is involved in this cytogenetic aberration. Additionally, we demonstrate the resulting overexpression of CCND1 on the RNA and protein level, thereby consolidating the new diagnosis of a MCL-like B-cell neoplasia. Summing up, we described a rare case of t(11;22)(q13;q11.2) in a MCL-like neoplasia and showed that this aberration leads to an overexpression of CCND1 which is regarded as a key biological feature in MCL. This case underlines the importance of cytogenetic analyses especially in atypical cases of B cell lymphomas.Molecular Cytogenetics 04/2011; 4(1):8.
Leukemia research 11/2010; 35(3):e25. · 2.36 Impact Factor