Table 2.

Molecular subtypes in T cell acute lymphoblastic leukemia, based on [28,29].

Subtype	Characteristics	Frequency	Dominant Genetic Abnormalities	Outcome
ETP (early T cell precursor)	Gene expression profile similar to hematopoietic stem cells and myeloid progenitors, with a high expression of self-renewal genes including LMO2/LYL1 HOXA, and BCL2	10%	Mutation of the JAK-STAT or Ras signaling pathways (e.g., FLT3, NRAS and JAK3), epigenetic regulators (e.g., EZH2, IDH1, IDH2, DNMT3A), genes involved in hematopoietic development (GATA3, ETV6, RUNX1, IKZF1), histone-modifying genes (EZH2, EED, SUZ12, SETD2 and EP300), and rearrangements of NUP98 and KMT2A genes	Can be effectively treated using early-response-based intensification
TLX3 (T-cell leukemia homeobox protein 3)	Lack a functional T-cell receptor (TCR) or presence of γ/δ TCR, rearrangements of the transcription factor TLX3	25%	High frequency of NOTCH1 mutations, and CDKN2A deletions. Mutations in CTCF, DNM2, PHF6, BCL11B, MYC, RPL5, RPL10, KDM6A and IL7R genes	Favorable
TLX1/NKX2.1 (T-cell leukemia homeobox protein 1/NK2 homeobox 1)	Genomic rearrangements involving either TLX1 or NKX2.1, CD1 expression, and differentiation arrest at the cortical stage, proliferative subtype	10%	TLX1 or NKX2.1 translocations	Excellent
TAL/LMO (transcription activator-like/LIM domain-only)	Ectopic expression of TAL1, TAL2, LYL1, LMO1, LMO2, or LMO3 and late cortical immunophenotype	40–60%	Mutations of PI3K signaling pathway (PTEN and PIK3R1), USP7 alterations, LEF1 deletions, SIL-TAL1 fusion	Poor

Abbreviations: BCL11B, BAF Chromatin Remodeling Complex Subunit; BCL2, BCL2 Apoptosis Regulator; CD1, cluster of differentiation 1; CDKN2A, Cyclin Dependent Kinase Inhibitor 2A; CTCF, CCCTC-Binding Factor; DNM2, Dynamin 2; DNMT3A, DNA Methyltransferase 3 Alpha; EED, Embryonic Ectoderm Development; EP300, Histone Acetyltransferase P300; ETV6, ETS Variant Transcription Factor 6; EZH2, Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit; FLT3, Fms Related Receptor Tyrosine Kinase 3; GATA3, GATA Binding Protein 3; HOXA, Homeobox A Cluster; IDH1, Isocitrate Dehydrogenase (NADP(+)) 1; IDH2, Isocitrate Dehydrogenase (NADP(+)) 2; IKZF1, IKAROS Family Zinc Finger 1; IL7R, Interleukin 7 Receptor; JAK3, Janus Kinase 3; JAK-STAT, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway; KDM6A, Lysine Demethylase 6A; KMT2A, Lysine Methyltransferase 2A; LEF1, Lymphoid Enhancer Binding Factor 1; LMO1, LIM Domain Only 1; LMO2/LYL1, LIM Domain Only 2/ Lymphoblastic Leukemia Associated Hematopoiesis Regulator 1; LMO3, LIM Domain Only 3; MYC, MYC Proto-Oncogene; NOTCH1, Notch Receptor 1; NRAS, Neuroblastoma RAS Viral Oncogene Homolog; NUP98, Nucleoporin 98 And 96 Precursor; PHF6, PHD Finger Protein 6; PI3K, Phosphoinositide 3-kinase; PIK3R1, Phosphoinositide-3-Kinase Regulatory Subunit 1; PTEN, Phosphatase And Tensin Homolog; Ras, Ras Family Small GTP Binding Protein; RPL10, Ribosomal Protein L10; RPL5, Ribosomal Protein L5; RUNX1, RUNX Family Transcription Factor 1; SETD2, SET Domain Containing 2; SIL-TAL1, STIL Centriolar Assembly Protein- TAL BHLH Transcription Factor 1 gene fusion; SUZ12, Suppressor Of Zeste 12 Protein Homolog; TAL1, TAL BHLH Transcription Factor 1; TAL2, TAL BHLH Transcription Factor 2; USP7, Ubiquitin Specific Peptidase 7.