International Consensus Classification of acute lymphoblastic leukemia/lymphoma

Abstract

The updated International Consensus Classification (ICC) of B-acute lymphoblastic leukemia (B-ALL) and T-acute lymphoblastic leukemia (T-ALL) includes both revisions to subtypes previously outlined in the 2016 WHO classification and several newly described entities. The ICC classification incorporates recent clinical, cytogenetic, and molecular data, with a particular emphasis on whole transcriptome analysis and gene expression (GEX) clustering studies. B-ALL classification is modified to further subclassify BCR::ABL1-positive B-ALL and hypodiploid B-ALL. Additionally, nine new categories of B-ALL are defined, including seven that contain distinguishing gene rearrangements, as well as two new categories that are characterized by a specific single gene mutation. Four provisional entities are also included in the updated B-ALL classification, although definitive identification of these subtypes requires GEX studies. T-ALL classification is also updated to incorporate BCL11B-activating rearrangements into early T-precursor (ETP) ALL taxonomy. Additionally, eight new provisional entities are added to the T-ALL subclassification. The clinical implications of the new entities are discussed, as are practical approaches to the use of different technologies in diagnosis. The enhanced specificity of the new classification will allow for improved risk stratification and optimized treatment plans for patients with ALL.

Keywords: B-lymphoblastic leukemia; B-lymphoblastic lymphoma; Gene expression clustering; T-lymphoblastic leukemia; T-lymphoblastic lymphoma.

Figure 1.. Gene expression clustering of B-ALL cases

The figure depicts two dimensional clustering using t-distributed stochastic neighbor embedding of whole transcriptome sequencing data from 2041 leukemia samples collected at diagnosis from children or adults with ALL. Cases are color coded by subtype. This approach, and much of the data, were first reported by Gu, et al. [18], and has been updated to include additional CDX2/UBTF cases following recent definition of this subtype.