Targeted High Throughput Sequencing in the Diagnosis of Pediatric Acute Leukemia

Acute leukemias are a heterogeneous group of hematologic malignancies. They result from clonal expansion of immature cells whose number is greater than 20% in bone marrow. Childhood acute leukemias are the most common pediatric malignancies. In Europe and the United states, they represent about 35% of childhood cancers. 80% of them are acute lymphoblastic leukemia (ALL) and 15-20% of acute myeloid leukemia (AML). Current treatments allow a cure in about 80% of ALL, while this level is only 50% in AML.Acute leukemia diagnosis is based on the multidisciplinary exploration of leukemia cells by different techniques: * Cellular: cytology, immunophenotyping and cytochemistry * Cytogenetic: conventional (karyotype) and molecular (FISH) cytogenetic * Molecular: RT-PCR and RQ-PCR Cytogenetic studies are performed at time of acute leukemia diagnosis. Indeed, the WHO 2008 classification of acute leukemia is based largely on the presence of recurrent cytogenetic and molecular abnormalities. The most frequent chromosomal aberrations have been associated with specific clinical and biological characteristics and are now used as diagnosis and prognostic markers. These chromosomal abnormalities affect genes involving in the leukemogenesis process. These rearrangements are of several types: * Fusion genes causing : * Repression of transcriptional activity of genes involved in differentiation of hematopoietic cells (AML1-ETO, PML-RARA…) * Deregulation of signal transduction pathway (eg BCR-ABL chimeric protein with constitutive tyrosine kinase activity) * Changing in the state of chromatin condensation resulting changes of transcription (MLL gene rearrangements in 11q23, MOZ en 8p11…) * Deregulation of genes expression: chromosomal rearrangements can sometimes induce deregulation of adjacent genes to the breakpoint. For example, inv(3)(q21q26) or t(3;3)(q21;q26) induce over expression of transcriptional factor EVI-1. * Loss of function due to deletion of variable size in gen