J Erika Haydu1, Adolfo A Ferrando. 1. Institute for Cancer Genetics and Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
Abstract
PURPOSE OF REVIEW: Early T-cell precursor (ETP) leukaemias have been recently recognized as a form of T-cell acute lymphoblastic leukaemia (T-ALL) with a poor prognosis. The purpose of this review is to outline the most recent advances in the biology, genetics and prognostic significance of this aggressive disease. RECENT FINDINGS: Detailed immunophenotypic analyses have defined ETP T-ALLs as a distinct group of T-ALL with a poor prognosis. Transcriptionally, ETP T-ALLs and early immature T-ALLs, a broader group of tumours characterized by very early arrest in T-cell differentiation, are most related to haematopoietic stem cells and myeloid progenitors. Consistently, these leukaemias show lower frequencies of prototypical T-ALL lesions such as CDKN2A/B deletions and activating mutations in NOTCH1 and show a higher prevalence of mutations typically associated with the pathogenesis of acute myeloid leukaemias (AMLs). SUMMARY: ETP and early immature T-ALLs are characterized by a very early differentiation arrest and show unique genetic and transcriptional features that overlap both with T-ALL and with AML. Given the unique biology and poor prognosis associated with the ETP T-ALL group, there is an urgent need of new tailored therapeutic strategies for the treatment of this disease.
PURPOSE OF REVIEW: Early T-cell precursor (ETP) leukaemias have been recently recognized as a form of T-cell acute lymphoblastic leukaemia (T-ALL) with a poor prognosis. The purpose of this review is to outline the most recent advances in the biology, genetics and prognostic significance of this aggressive disease. RECENT FINDINGS: Detailed immunophenotypic analyses have defined ETP T-ALLs as a distinct group of T-ALL with a poor prognosis. Transcriptionally, ETP T-ALLs and early immature T-ALLs, a broader group of tumours characterized by very early arrest in T-cell differentiation, are most related to haematopoietic stem cells and myeloid progenitors. Consistently, these leukaemias show lower frequencies of prototypical T-ALL lesions such as CDKN2A/B deletions and activating mutations in NOTCH1 and show a higher prevalence of mutations typically associated with the pathogenesis of acute myeloid leukaemias (AMLs). SUMMARY:ETP and early immature T-ALLs are characterized by a very early differentiation arrest and show unique genetic and transcriptional features that overlap both with T-ALL and with AML. Given the unique biology and poor prognosis associated with the ETP T-ALL group, there is an urgent need of new tailored therapeutic strategies for the treatment of this disease.
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