MISSION STATEMENT
The Diagnostic Center of Acute Leukemia (DCAL) is situated at the Medical Campus of the Goethe-University in Frankfurt / Main, Germany.
We are investigating chromosomal translocations of the human MLL gene, associated with high-risk acute leukemia (AML and ALL) of pediatric and adult leukemia patients. By applying a novel "long distance inverse PCR method" (LDI-PCR), we are able to identify MLL gene rearrangements at the genomic DNA level of pre-screened patients (Meyer et al., PNAS 2005).
Due to our investigations, a total of 77 translocation partner genes can now be annotated, of which 34 were identified in the last 7 years at the DCAL. However, about more than 20 translocation partner genes are still unknown and await their discovery.
The method allows large scale analyses. As an important result, patient-specific biomarker sequences will be obtained that allow precise MRD studies to monitor leukemia patients during and after therapy. These reliable molecular biomarkers help to optimize treatment and outcome of acute leukemia patients (see Burmeister et al., Blood 2006; Burmeister et al., Blood 2009; van der Velden et al., Leukemia 2009). To date more than 1.600 genomic breakpoints of acute leukemia patients have been successfully analyzed @ the DCAL.
FURTHER DEVELOPMENTS
Since Jan 2008, we are offering additional services upon request. Genomic breakpoint analysis can be done by Assymetric Long Distance Multiplex PCR for PML•RARalpha [t(15;17)] and CBFbeta-MYH11 [Inv(16)]. We are also involved in projects aiming to clone TEL or BMF deletions, cloning TEL-AML1 and TEL-ABL breakpoints, PAX5-ETV6 breakpoints and IgH rearrangements in lymphoma patients. For BCP-ALL patients, we provide support for the analysis of gene-internal deletions of IKAROS which can be used as MRD markers. For solid tumor patients we have cloned a novel BRAF fusion in polycytic astrocytoma and the novel MLH1-ITGA9 fusion in a LYNCH syndrome kindred.
We are currently cloning all novel MLL fusion genes into a pMSCV retroviral backbone for transduction/transplantation experiments if murine hematopoietic cells. For further informations or collaborations, please contact Prof. Rolf Marschalek (see contact informations).