T‐cell acute lymphoblastic leukaemia: recent molecular biology findings

Abstract

Summary For many years, T‐cell acute lymphoblastic leukaemia (T‐ALL) has been considered and treated as a single malignancy, but divergent outcomes in T‐ALL patients receiving uniform treatment protocols encouraged intensive research on the molecular biology of this disease. Recent findings in the field demonstrate that T‐ALL is much more heterogeneous than originally believed and extremely diverse outcomes of patients require refinement of T‐ALL classification, leading to subtype‐specific adjustment of treatment. Many different biological features of T‐ALL blast cells have recently been found to contribute to disease development and patient outcome and their analysis could potentially be introduced into improved diagnostics and classification of the disease. This review focuses on five key issues of T‐ALL biology: chromosome aberrations, gene expression profiles, gene mutations, DNA methylation patterns, and immunoglobulin/T cell receptor (Ig/TCR) gene rearrangements. Additionally, molecular monitoring of minimal residual disease, by far the most reliable independent prognostic factor in T‐ALL, has been highlighted in the context of Ig/TCR gene rearrangements. Translation of this biological information into better prognostic classification and more effective treatment should lead to improvement of outcome in T‐ALL patients.

Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line

“…Despite markedly improved survival rates, the prognosis remains poor for some group of patients [5]. The cure rate for T-cell ALL, comprising about 15% of pediatric ALL, is lower compared to B-cell ALL, but recently the outcome for patients with T-cell ALL also improved significantly with high dose dexamethasone during remission induction [6,7].…”

The TCR γδ Repertoire and Relative Gene Expression Characteristics of T-ALL Cases with Biclonal Malignant Vδ1 and Vδ2 T Cells

“…The c based on the clinical finding that both the T-ALL cases, clinical outcome of T-ALL after chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively different: even some cases with good outcome and long-term survival undergo disease relapse, and some de novo cases with poor prognosis, who have had unsuccessful treatment, die due to rapid disease progression and complications (Aifantis et al, 2008;Kraszewska et al, 2012;Van Vlierberghe et al, 2013). This high failure rate is mainly due to an insufficient understanding of T-ALL biology, which hampers the identification of reliable prognosis factors that may enable appropriate therapy adjustment (Kraszewska et al, 2012).…”

“…The c based on the clinical finding that both the T-ALL cases, clinical outcome of T-ALL after chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively different: even some cases with good outcome and long-term survival undergo disease relapse, and some de novo cases with poor prognosis, who have had unsuccessful treatment, die due to rapid disease progression and complications (Aifantis et al, 2008;Kraszewska et al, 2012;Van Vlierberghe et al, 2013). This high failure rate is mainly due to an insufficient understanding of T-ALL biology, which hampers the identification of reliable prognosis factors that may enable appropriate therapy adjustment (Kraszewska et al, 2012). Numerous genes were identified as predictors or related to the poor prognosis of T-ALL, for example, MLLT10 was shown to predict poor prognosis in many T-ALL cases, and TAL1 and HOX11L2 rearrangements have been associated with trends toward good and poor outcomes, respectively, while Notch1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage (van Grotel et al, 2006;van Grotel et al, 2008;Kraszewska et al, 2012;Lin et al, 2012).…”

“…This high failure rate is mainly due to an insufficient understanding of T-ALL biology, which hampers the identification of reliable prognosis factors that may enable appropriate therapy adjustment (Kraszewska et al, 2012). Numerous genes were identified as predictors or related to the poor prognosis of T-ALL, for example, MLLT10 was shown to predict poor prognosis in many T-ALL cases, and TAL1 and HOX11L2 rearrangements have been associated with trends toward good and poor outcomes, respectively, while Notch1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage (van Grotel et al, 2006;van Grotel et al, 2008;Kraszewska et al, 2012;Lin et al, 2012). Moreover, complex acquired genetic aberrations, including chromosomal translocations, gene rearrangements, and mutations resulting in the abnormal expression of oncogenes may be associated with advanced disease and resistance to treatment.…”

“…In addition, secondary T-ALL following AML has been also reported (Liso et al, 1998). Despite significant improvement in our understanding of T-ALL biology and pathogenesis, many questions remain unanswered, and many new ones arise (Kraszewska et al, 2012). For example, little is known about the characteristics of T-ALL cases with two malignant T-cell clones.…”