TALLSorts: a T-cell acute lymphoblastic leukemia subtype classifier using RNA-seq expression data

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematologic malignancy affecting both children and adults. 1,2 T-ALL subtype identification is an emerging area of active research; as recently as 2016, the World Health Organization suggested only 1 provisional distinct T-ALL classification: the early T-cell precursor (ETP). 3wever, recent revisions by the International Consensus Classification in 2022 further subclassified ETP based on BCL11B deregulation while introducing 8 provisional classifications for non-ETP T-ALL. 4,5These include subtypes characterized by rearrangements in TAL1/2, TLX1, TLX3, LMO1/2, SPI1, NKX2, and BHLH and dysregulation of HOXA. 4,5Other recent work by Dai et al, using gene expression analysis of 8 international cohorts of T-ALL samples from adult and pediatric patients, similarly developed classifications based on molecular abnormalities in TAL1, TLX1, TLX3, NKX2, LMO1/2, LYL1, and SPI1 while subclassifying HOXA-dysregulated samples based on the presence of KMT2A or MLLT10 fusions, 6 resulting in 10 subtypes.Furthermore, Brady et al recently described 10 subtypes, defined again by TAL1/2, TLX1, TLX3, NKX2, LMO1/2, SPI1, and HOXA abnormalities, along with BCL11B abnormalities 7 and an otherwise nonspecified group.