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Br J Haematol. 2019 May 22. doi: 10.1111/bjh.15960. [Epub ahead of print]

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

Author information

1
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
5
School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

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.

KEYWORDS:

CD10; CD33; T-cell; flow cytometry; immunophenotype; lymphoblastic leukemia/lymphoma; targeted therapy

PMID:
31115909
DOI:
10.1111/bjh.15960

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