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Early T precursor acute lymphoblastic leukaemia/lymphoma shows differential immunophenotypic characteristics including frequent CD 33 expression and in vitro response to targeted CD 33 therapy
Author(s) -
Khogeer Haitham,
Rahman Haitham,
Jain Nitin,
Angelova Evgeniya A.,
Yang Hong,
Quesada Andres,
Ok Chi Y.,
Sui Dawen,
Wei Peng,
Al Fattani Areej,
Pierce Sherry,
Loghavi Sanam,
Lamb Audrey,
Hu Peter,
Thakral Beenu,
KanagalShamanna Rashmi,
Jorgensen Jeffrey L.,
Jabbour Elias J.,
Kantarjian Hagop M.,
Medeiros L. Jeffrey,
Khoury Joseph D.
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15960
Subject(s) - immunophenotyping , medicine , lymphoma , flow cytometry , immunology
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 CD 2, CD 10, CD 33 and TdT between ETP ‐ ALL and non‐ ETP ‐ ALL . Positive CD 33 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‐ CD 33 therapy with IMGN 779 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. CD 33 expression is frequent in ETP ‐ ALL , and in vitro data suggest that exploring anti‐ CD 33 therapy in ETP ‐ ALL is warranted.