ETP-ALL (Early T-cell precursor acute lymphoblastic leukemia)

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ETP-ALL is currently defined by a distinctive phenotype characterized by a lack of expression of the T-lineage cell surface markers CD1a and CD8, weak or absent expression of CD5 and aberrant expression of one or more myeloid or stem cell markers (Coustan-Smith et al., 2009).
Early T-cell precursors (ETPs) are immature progenitors that have recently immigrated from the bone marrow to the thymus and which retain a multilineage differentiation potential (T-lymphoid, natural killer, dendritic and myeloid cell differentiation potential).

There is currently no consensus on the prognosis of ETP-ALL. Initial prognostic studies between 2009 and 2012 reported a negative prognostic impact on response rate and survival (Coustan-Smith et al., 2009, Inukai et al., 2012; Ma et al., 2012) and a higher risk of relapse (Allen and al., 2013).

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Immunophenotyping:

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ETP-ALL cases are currently identified through the phenotype of blast cells : CD1a-, CD8-, CD5- /weak, and positivity for one or more stem cell and/or myeloid antigens (CD117, CD34, HLA-DR, CD13, CD33, CD11b, and/or CD65). ETP-ALL typically also express CD2, CD7 and cytoplasmic CD3 and may express CD4.

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                                                                                                                     CASE 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In case 1 blasts are gated from CD45 population in red. these blasts are positive for cCD3 , MPO , CD7, CD34CD117, CD38, CD2, CD11B and CD13dim while negative for CD5, CD33, HLA-DR, CD123, CD1a, CD56, CD19, CD22, CD16 and Tdt.

 

 

 

 

                                                                                                                     CASE 2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In case 2 blasts are gated from CD45 population in red. these blasts are positive for cCD3, CD7, CD34, CD33, CD117dim, CD2, CD11B, HLA-DR  while negative for CD5, CD1a, CD56, CD19, CD65, cCD79a, CD8 and CD4.

 

 

 

REFERENCES

1. Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Groupfor the Immunological Characterization of Leukemias (EGIL). Leukemia . 1995;9(10):1783-1786.

2. Ludwig WD, Raghavachar A, Thiel E. Immunophenotypic classification of acute lymphoblastic leukaemia. Baillieres Clin Haematol. 1994;7(2):235-262.

3. Ludwig WD, Reiter A, Loffler H, et al. Immunophenotypic features of childhood and adult acute lymphoblastic leukemia (ALL): experience of the German Multicentre Trials ALL-BFM and GMALL. Leuk Lymphoma. 1994;13 Suppl 1:71-76.

4. Borowitz MJ, Chan JKC. T Lymphoblastic Leukemia/Lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of Tumours of Haematopoietic and LymphoidTissues. Lyon: IARC; 2008:176-178.

5. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147-156.

6. Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157-163.

7. Bell JJ, Bhandoola A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature. 2008;452(7188):764-767.

8. Conter V, Valsecchi MG, Buldini B, et al. Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. Lancet Haematol. 2016;3:e80-e86.

9. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10:147-156.

10. Patrick K, Wade R, Goulden N, et al. Outcome fro children and young people with Early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol. 2014;166:421-424.

11. Wood BL, Winter SS, Dunsmore KP, et al. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early thymic precursor (ETP) immunophenotype, and validation of the prognostic value of end-induction minimal residual disease (MRD) in children's oncology group (COG) study AALL0434. Blood. 2014;124:1.