T Cell Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) was diagnosed in 64,190 people globally in 2017,1 and is the most common pediatric cancer. It is divided into two subcategories – B cell ALL (B-ALL) and T cell ALL (T-ALL) – with the latter representing a much smaller fraction of all cases. T-ALL is a highly aggressive form of cancer, however, recent advances in treatment strategies have radically improved prognoses for pediatric patients. Unfortunately, this is not reflected in adults, with the five-year survival rate for T-ALL patients declining significantly with increasing age.2

Formation

T-ALL is a blood malignancy characterized by the production and accumulation of immature T cell lymphoblasts in the blood and bone marrow. Genetic abnormalities in hematopoietic lymphoid precursors result in their impaired maturation, leading to the generation of abnormal lymphoblasts and atypical cells, which accumulate in the bone marrow, peripheral blood, and other tissues. These cells suppress regular hematopoiesis in the bone marrow, collect in the lymphatic system causing lymphadenopathy, and release inflammatory mediators.

Diagnosis and treatment assessment

Initial blood tests to diagnose T-ALL may show the presence of abnormal lymphoblasts, but a definitive diagnosis depends on the presence of at least 20% lymphoblasts in the bone marrow or blood. Further diagnostic and prognostic tests to stratify patients include evaluation for morphology, flow cytometry, immunophenotyping, and cytogenetic testing.3

T cell acute lymphoblastic leukemia

Figure 1. Example micrograph of an acute lymphoblastic leukemia.8

Historically, treatment response was assessed morphologically3 but, more recently, minimal residual disease (MRD) monitoring – describing the number of cancer cells remaining after treatment – has been used to increase accuracy, and to guide subsequent therapeutic choices. ALL is the first neoplastic disease where MRD monitoring has been included as a fundamental tool to guide therapy in this way.4 The most common methods include multi-parametric flow cytometry (MFC) of leukemia-associated immunophenotypes and PCR based tools, which detect one leukemic cell among 10,000 normal cells – or 10-4 – to provide the required sensitivity.4 MRD with conventional flow cytometry, for example, gives rapid information about a sample at a cellular level, and offers sensitivity of 10-4 when performed with eight to ten colors.5

Cell markers

The analysis of most leukemias involves the bone marrow, which expresses increasing levels of CD45 as the disease matures. Lymphoblast infiltration of the bone marrow is best recognized on a CD45 versus side-scatter plot, compared to traditional forward side-scatter gating.6 Other surface markers that have been identified include nuclear terminal deoxynucleotidyl transferase (NuTdT), cytoplasmic CD3 (cyCD3), surface-membrane CD3 (SmCD3), CD2, CD4, CD5, CD7, CD8, CD1a, CD44, and CD99.6, 7

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References

  1. Yi M, Zhou L et al. (2020) Global burden and trend of acute lymphoblastic leukemia from 1990 to 2017. Aging. 12(22):22869-22891. doi:10.18632/aging.103982
  2. Guru Murthy GS, Pondaiah SK et al. (2019) Incidence and survival of T-cell acute lymphoblastic leukemia in the United States. Leuk Lymphoma. 60(5):1171-1178. doi:10.1080/10428194.2018.1522442
  3. Terwilliger T, Abdul-Hay M. (2017) Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 7(6). doi:10.1038/bcj.2017.53
  4. Della Starza I, Chiaretti S et al. (2019) Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances. Front Oncol. 9:726. doi:10.3389/fonc.2019.00726
  5. Van Dongen JJ, van der Velden VH et al. (2015) Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 125(26):3996-4009. doi:10.1182/blood-2015-03-580027
  6. Jennings CD, Foon KA. (1997) Recent Advances in Flow Cytometry: Application to the Diagnosis of Hematologic Malignancy. Blood. 90(8):2863–2892. doi:10.1182/blood.V90.8.2863
  7. Ikoma-Colturato MRV, Beltrame MP et al. (2021) Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation. Hematol Transfus Cell Ther. 43(3):332-340. doi:10.1016/j.htct.2020.09.148 
  8. https://www.istockphoto.com/fr/photo/aiguë-lymphoblastic-leucémie-all-gm481284138-69213451

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