Developing new technologies and genomic techniques generate big data, which is very helpful to evaluate extensively hematologic malignancies. Besides wet lab results, such as gene and microRNA expression, methylation profile, next-generation sequencing data, whole-exome and RNA-seq, FISH analysis, SNP arrays, new computer algorithm, and programs have allowed for improving the understanding transformation oncohematological disorder mechanism. In addition to that, the whole wet and dry lab results permit us to develop a new prognostic algorithm, which can assist to decide the most appropriate treatment. Furthermore, finding and analyzing new biomarkers drive the geneticists to produce therapy target and personalized medicine. The novel and effective contribution of the new technologies in the context of leukemia of both AML, Acute Myeloid Leukemia and ALL, Acute Lymphoblastic Leukemia and genomic characterization of de novo mixed-lineage leukemia are described in this review.