Classification of Acute Leukemias – Past, Present, and Future

The perspective of the classification of any disease is to treat them according to their biologic behavior. Standard criteria to distinguish between myeloid and lymphoid acute leukemias were laid down as the first of its kind, by the French-American-British (FAB) working group. The FAB classification had a cursory correlation with clinical outcome, poor concordance owing to inter-observer variation, and failure to incorporate cytogenetic data. Hence, the World Health Organization (WHO) classification of leukemias evolved in 1997 with the goal of improving the objectivity and reproducibility, which had incorporated cytogenetic abnormalities and immunology as principal designating criteria, other than the morphology. Major changes were made in the subsequent editions of WHO classification, incorporating newer genetic abnormalities such as mutations of nucleophosmin member 1, CCAAT/enhancer-binding protein alpha; renaming of the existing classes, etc. The role of the genes encoding guanine nucleotide-binding protein gamma 11, amphiregulin, and ceruloplasmin; the biomarkers platelet factor 4 and connective tissue-activating peptide III, complement fragment C3a; the mRNA coding for plexin C1, leukotriene B4 receptor 1, and Immunoglobulin superfamily member 2; mixed lineage leukemia gene rearrangement in the prognosis of leukemias is proven. Thus, the approach of diagnostics using cytogenetics and immunophenotyping may further be modified.