LUCIA BRANDIMARTE. New genomic technologies for a personalized diagnosis
of Acute Lymphoblastic Leukemia. Background. Acute Lymphoblastic ...
LUCIA BRANDIMARTE New genomic technologies for a personalized diagnosis of Acute Lymphoblastic Leukemia Background Acute Lymphoblastic Leukemia (ALL) is a hematologic malignancy whose variability of prognosis emphasizes the heterogeneity of molecular mechanisms that are involved in its origin and progression. Karyotyping in ALL originally identified chromosomal abnormalities that are today the basis of prognosis,1 even though 50% of cases are still classified as ''intermediate''. Nowadays evaluation of minimal residual disease (MRD) during the induction and consolidation, as assessed according to Ig or TCR gene rearrangements at diagnosis, provides the best prognostic stratification, particularly in children. New markers are however needed because MRD can be assessed only in the course of treatment. New genomic technologies (i.e. array, SNPs, Gene Expression Profiling, Next Generation Sequencing) have identified a variety of new cryptic molecular lesions in ALL and provided new perspectives for classification.2 The translational perspective of this project is to apply this information in diagnostic programs. Aims •
To study new genes and molecular mechanisms that emerge from the genomic characterization of large series of adults and children with B- and T-ALL;
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To apply new genomic knowledge in the creation and validation of diagnostic algorithms. Methods
In this project, the following genomic technologies will be applied: karyotyping, Fluorescence in Situ Hybridization (especially CI-FISH), metaphase Comparative Genomic Hybridization (CGH), microarrays-CGH, expression microarrays, Denaturing High Performance Liquid Chromatography (DHPLC), Sanger sequencing, SNPs analysis and deep-sequencing (Illumina). Expected results Through extensive use of new technologies we expect to uncover unknown genes and leukemogenic mechanisms in ALL and integrate these findings into diagnostic pathways to improve disease classification and prognostic stratification. Our ultimate aim is to provide each patient with a genetic identity card that fine-tunes individualized prognosis at diagnosis and identifies potential target therapies. References 1) Pui CH et al. New England Journal of Medicine. 2004;350(15):1535-48 2) Strefford JC et al. Oncogene. 2007;26(29):4306-18
