Immunophenotypic analysis of T‐acute lymphoblastic leukemia. A CD5‐based ETP‐ALL perspective of non‐ETP T‐ALL

Abstract

T-cell antigens [CD5,CD1a,CD8] define early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). To understand immature T-ALL of which ETP-ALL is part, we used these antigens to subcategorize non-ETP T-ALL for examining expression of myeloid/stem cell antigens (M/S) and clinical features. Using CD5 (+/-) to start categorization, we studied 69 routinely immunophenotyped patients with T-ALL. CD5(-) was a homogenous (CD8,CD1a)(-) M/S(+) ETP-ALL group (n = 9). CD5(+) cases were (CD8,CD1a)(-) pre-T-ALL (n = 22) or (CD8,CD1a)(+) (n = 38) thymic/cortical T-ALL; M/S(+) 20/22 (90.91%) in former and 22/38 (57.89%) in latter (P = 0.007). ETP- and pre-T-ALL together (CD1a(-) ,CD5(-/+) immature T-ALL group) were nearly always M/S(+) (29/31; 93.55%). In multivariate analysis, only ETP-ALL predicted poor overall survival (P = 0.02). We conclude (i) CD5 negativity in T-ALL almost always means ETP-ALL. CD1a and CD8 negativity, as much as CD5, marks immaturity in T-ALL, and the CD5(+/-) /CD1a(-) /CD8(-) immature T-ALL group needs further study to understand the biology of the T-ALL-myeloid interface. (ii) ETP-ALL patients may be pre-T-ALL if CD2(+) ; CD2(+) , conversely, CD5(-) /CD1a(-) /CD8(-) pre-T ALL patients are ETP-ALL. (iii) Immunophenotypic workup of T-ALL must not omit CD1a, CD5, CD8 and CD2, and positivity of antigens should preferably be defined as recommended for ETP-ALL, so that this entity can be better evaluated in future studies of immature T-ALL, a group to which ETP-ALL belongs. (iv) ETP-ALL has poor prognosis.

Early T precursor acute lymphoblastic leukaemia/lymphoma shows differential immunophenotypic characteristics including frequent CD33 expression and in vitro response to targeted CD33 therapy

“…Given that the level of CD5 expression tends to be difficult to ascertain in a subset of T‐ALL, we believe that determining the T‐ALL immunophenotypic score could offer added value at this decision node. This approach is favoured over the use of CD5 as an initial decision node in the subclassification of T‐ALL (Chopra et al , ). Determining this scoring system by using immunohistochemistry seems warranted, but was not evaluated in this study.…”

DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T‐Cell Acute Lymphoblastic Leukemia

“…The immature subgroup of T‐ALL described by Coustan‐Smith et al. as “early T‐cell precursor” (ETP) is characterized by hematopoietic stem cell (HSC) and myeloid progenitor markers …”

“…The European Group for the Immunological Classification of Leukemias (EGIL) criteria were used as defined by Bene et al [3] The immature subgroup of T-ALL described by Coustan-Smith et al [15] as "early T-cell precursor" (ETP) is characterized by hematopoietic stem cell (HSC) and myeloid progenitor markers. [3,[15][16][17] Publicly available methylation data (NCBI GEO database, GSE49618) of sorted T-cells (CD3 + ) and HSCs (CD34 + , CD38 -) from healthy donors were used as reference samples in the methylation heat map ( Fig. 1A) to illustrate methylation profiles of normal immature and mature hematopoietic cells.…”

Immunophenotypic characteristics of early T-cell precursor acute lymphoblastic leukemia

“…Исследование позволило выявить очевидную иммунофенотипическую гетерогенность среди пациентов этой группы: выявлены разные профили коэкспрессирующихся маркеров и уровни их экспрессии. В более ранних исследованиях ETP-ОЛЛ считали подтипом исключительно TI-ОЛЛ, позже эти данные были опровергнуты [21,22]. Мы тоже обнаружили различные варианты Т-ОЛЛ, которые удовлетворяют иммунофенотипическим критериям ETP-ОЛЛ (рисунки 3-7).…”