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

Abstract

Summary The differential immunophenotypic characteristics of early T precursor (ETP) acute lymphoblastic leukaemia/lymphoma (ALL) remain incompletely characterized. The study group (n = 142) included 106 (74·7%) men and 36 (25·3%) women with a median age of 34·9 years (range, 2–79) at diagnosis. Patients were subtyped by flow cytometry immunophenotyping as follows: 33 (23·2%) ETP; 32 (22·5%) early non‐ETP; 60 (42·2%) thymic; and 17 (12·1%) mature. Excepting definitional markers, there was a significant differential expression of the markers CD2, CD10, CD33 and TdT between ETP‐ALL and non‐ETP‐ALL. Positive CD33 expression (≥20% of leukaemic blasts) was detected in 21/33 (63%) ETP‐ALL compared with 17/95 (17·9%) non‐ETP‐ALL (P < 0·001). Notably, targeted anti‐CD33 therapy with IMGN779 resulted in significant growth inhibition and increased apoptosis in ETP‐ALL cells in vitro. An 11‐marker T‐ALL immunophenotype score discriminated reliably between ETP and non‐ETP ALL. Longitudinal analysis of ETP‐ALL cases in this study demonstrated that the immunophenotype may be occasionally dynamic but is largely stable over the disease course. In summary, identification of ETP‐ALL might be enhanced by using an 11‐marker T‐ALL immunophenotype score. CD33 expression is frequent in ETP‐ALL, and in vitro data suggest that exploring anti‐CD33 therapy in ETP‐ALL is warranted.

Early precursor T-cell acute lymphoblastic leukemia: current paradigms and evolving concepts

“…18 Scoring schemas based on immunophenotypic profiles have been reported in an attempt to distinguish ETP-ALL from other leukemias. 7,9,19 Notably, it may be challenging to distinguish ETP-ALL from mixed phenotype acute leukemia. 6 ETP-ALL is uncommon (reports of ETP range from 5% to 36% in T cell ALL series/studies).…”

“…The CD33 and CD123 may be positive and appear to be so more frequently compared with non-ETP-ALL. 8,9 Interestingly, ETP-ALL with co-expression of B-cell markers has been reported, but the numbers of patients were small. 10 The clinical significance of B-cell marker expression is unclear.…”

CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies

“…Angelova and colleagues detected CD123 expression in 43.3% of T-ALL, with the vast majority of cases (92.3%) having early T precursor (ETP) or early non-ETP immunophenotype [23(Khogeer, 2019 #136)(Jain, 2016 #134)] [ 53 , 54 ]. Notably, their findings, in line with those reported by others [ 2 ], indicated that CD123 expression on leukemic cells in T-ALL was at a lower MFI compared to B-ALL.…”

Low LEF1 expression is a biomarker of early T-cell precursor, an aggressive subtype of T-cell lymphoblastic leukemia

“…As one of the routine examinations, the expression of relevant cell surface markers was measured by the flow cytometry [7]. However, the diagnosis can be varied depending on different pathologists and/or different parameters, for instance, the voltage setting.…”

“…However, the diagnosis can be varied depending on different pathologists and/or different parameters, for instance, the voltage setting. In order to improve the reliability of the diagnosis, Khogeer et al developed a scoring system based on 11 surface markers to re-define the ETP subgroup [7]. Still, it is solely based on the measurement a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 of flow cytometry.…”