representing approximately 15% of T-ALL overall, with an intermediate prognosis. It is defined by the
expression of CD7, the absence of CD1a and CD8 and positivity for at least one myeloid/stem cell
marker. ETP ALL also has a unique molecular profile with myeloid associated gene mutations occurring
far more often than T-cell associated mutations.19 While initial reports demonstrated poor outcomes
for ETP ALL, recent larger series have reported outcomes in ETP ALL in children that are similar to those
observed in non-ETP T-ALL.13,20-22
Comprehensive genomic analyses have recently identified recurrently mutated pathways across
molecularly defined subtypes of T-ALL.23 While some pathways were deregulated across all subtypes,
significant associations between mutated genes, pathways, and individual subtypes have been
observed, suggesting that different signaling pathways have distinct roles according to maturational
stage. An example of how genetic data may be incorporated into risk stratification in the future is the
oncogenetic classifier used by the FRALLE group based on NOTCH, PTEN and RAS mutational status.24
The classifier was used in combination with WBC and MRD to stratify patients into low, intermediate
and high risk groups. Notably, a very low risk group with a 5-year cumulative incidence of relapse (CIR)
of only 2% and DFS 98.3%, as well as a very high risk group of patients harboring a WBC count
>200,000/μL, a high risk genetic profile, and MRD >10-4, with a 5-year CIR of 46% and DFS 37.3%, were
identified. While this oncogenetic classifier awaits more broad scale validation, this is illustrates the
potential of genetics to augment T-ALL risk classification.
In conclusion, T-ALL is clinically and biologically unique and with advances in frontline therapy,
outcomes for T-ALL now approach those observed in B-ALL. Late time point MRD response is currently
the most important prognostic factor in T-ALL but risk assessment in the future is very likely to include
the addition of biological factors.
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