[6] Its clinical presentation most commonly includes infiltration of the central nervous system (CNS, i.e. brain and spinal cord), and is often associated with a mediastinal mass that originates from the thymus, as well as extramedullary involvement of multiple organs (particularly lymph nodes) as a result of hyperleukocytosis.

The most common clinical feature among patients is the proliferation of malignant clones, suppressing normal haematopoiesis and resulting in a deficiency of functioning peripheral blood cells, particularly thrombocytes.

[1] Basic karyotyping has shown structural chromosomal rearrangements in 50-75% of T-ALL patients, primarily involving inversions and translocations.

[1] Diagnostic yield can be substantially increased through other methods such as fluorescent in situ hybridization (FISH) and various molecular technologies, for example, single nucleotide polymorphism (SNP) arrays.

[4] Karyotyping has shown that TRD and TRB undergo recombination most commonly, whereas TRA is seldom involved, and TRG is rarely rearranged.

These rearrangements affect the normal process of TCR formation and can lead to the failure of cellular machinery to correctly repair recombination-activating gene (RAG) protein-induced double-strand breaks.

[1] The build-up of malignant T-cells in T-ALL consists of clones with identical TCR gene arrangements originating from a single cell.

This leads to the dysregulation of partner gene transcription, serving as the main cause of leukemogenesis – a multi-step process of induction, development, and progression of leukemic diseases.

Like most cancers, mutations in DNA lead to the development of T-cell acute lymphoblastic leukemia (T-ALL) and loss of function in white blood cells.

[10] Some patients may have familial histories with leukemia predispositions, increasing the risk of developing T-ALL[citation needed].

Li–Fraumeni syndrome is an inherited condition that leads to mutations in TP53, a tumour suppressor gene, thereby increasing the risk of T-ALL.

Bone marrow aspiration and biopsies are typically done simultaneously to help determine and confirm the type and severity of T-ALL.

[2] Since a swollen spleen and lymph nodes are symptoms of T-ALL, X-rays and ultrasound scans, such as CT and MRI, can help confirm the diagnosis.

Central Nervous System Involvement T-ALL can spread to the brain and spinal cord,[2] which can be diagnosed through lumbar puncture assessment.

[1] For high-risk T-ALL patients, allogeneic hematopoietic stem cell transplantation has shown highly successful and promising results.

Patients undergoing transplantation must be continuously monitored for minimal residual disease (MRD), usually via qPCR analysis of T-cell receptor (TCR) genes to evaluate for fusion transcripts such as SIL-TAL1.

Studies have shown that administering either a traditional paediatric regimen or intensive block-based chemotherapy yields significantly different responses.

[1] Monitoring for minimal residual disease (MRD) via qPCR analysis is critical, as mentioned previously, to evaluate the efficacy of treatment.

Recent genomic studies have identified a selection of genetic variants related to clonal evolution that drive resistance, which serve as the basis for T-ALL relapse.

Thus, the multistep progenesis of T-ALL has been said to intensify and rapidly progress due to accumulation of effects resulting from dysregulation of multiple signalling pathways.