Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets

Abstract

A wide range of immature acute leukemias (AL), ranging from acute myeloid leukemias with minimal differentiation to acute leukemias with an ambiguous lineage, i.e., acute undifferentiated leukemias and mixed phenotype acute leukemia with T- or B-plus myeloid markers, cannot be definitely assigned to a single cell lineage. This somewhat “grey zone” of AL expresses partly overlapping features with the most immature forms of T-cell acute lymphoblastic leukemia (T-ALL), i.e., early T-cell precursor ALL (ETP-ALL), near-ETP-ALL, and pro-T ALL. These are troublesome cases in terms of precise diagnosis because of their similarities and overlapping phenotypic features. Moreover, it has become evident that they share several genomic alterations, raising the question of how their phenotypes reflect distinct AL entities. The aim of this review was to provide a systematic overview of the genetic events associated with immature T-ALL and outline their relationship with treatment choices and outcomes, especially looking at the most recent preclinical and clinical studies. We wish to offer a basis for using the genetic information for new diagnostic algorithms, in order to better stratify patients and improve their management with more efficient and personalized therapeutic options. Understanding the genetic profile of this high-risk T-ALL subset is a prerequisite for changing the current clinical scenario.

Modern treatment approaches to adult acute T-lymphoblastic and myeloid/T-lymphoblastic leukemia: from current standards to precision medicine

“…Heterogeneous group accounting for 15% of childhood and 25% of adult T-ALLs [21,38–40,41 ▪▪ ]. In 40–45% of immature cases the poor prognostic HOXA-positive subgroup is marked by rearrangements at HOXA cluster or at NUP214 , NUP98 , MLLT10 , and KMT2A gene, in a mutually exclusive manner [42–46].…”

“…In 40–45% of immature cases the poor prognostic HOXA-positive subgroup is marked by rearrangements at HOXA cluster or at NUP214 , NUP98 , MLLT10 , and KMT2A gene, in a mutually exclusive manner [42–46]. HOXA alterations are typically associated with deletions of TCF7 , RB1 and/or TP53 , and high incidence of mutations affecting members of the JAK/STAT pathway, such as JAK3, STAT5B, and IL7R [20,21,27 ▪ ,41 ▪▪ ]. Furthermore, while CDKN2AB deletions are relatively rare (25%), CDKN1B deletions are frequent (>50%).…”

Comparison of flowcytometry‐based scoring system for the diagnosis of early T precursor‐acute lymphoblastic leukemia

“…Blasts may express CD2 and CD4, but these antigens are not required. If CD5 is positive, then it should be expressed in less than 75% of blast cells (Genescà & la Starza, 2022).…”

“…If CD5 is positive, then it should be expressed in less than 75% of blast cells (Genescà & la Starza, 2022).…”

The progress in the relationship between trace elements and acute lymphoblastic leukemia

“…As the most common childhood cancer, acute lymphoblastic leukemia (ALL) accounts for 26% of tumors in children under 15% and 8% in adolescents between 15–19 years of age ( Ward et al, 2014 ). ALL is an aggressive and complex disease, and the epidemiological survey data showed that its age-standardized incidence is 0.68/1000,000 ( Yi et al, 2020 ; Genescà and González-Gil, 2022 ). ALL stands for T/B precursor lymphocyte malignancy and blocks lymphocyte differentiation, allowing cells to proliferate and survive abnormally ( Zuckerman and Rowe, 2014 ).…”