Terminal deoxynucleotide transferase (TdT) is a special deoxyribonucleic acid (DNA) polymerase. It can bind a single deoxynucleotide to the 3′-OH end of a DNA molecule in the absence of a template. TdT is a specific intracellular marker of immature lymphocytes in the hematopoietic system, which is of great significance in the diagnosis of lymphoid tumors. The diagnosis of lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) depends on immunotyping. TdT is usually positive in LBL/ALL, which is an important basis for clinical diagnosis of LBL/ALL. TdT-negative LBL/ALL is rare in clinical practice. Because of its strong specificity in diagnosis, negative TdT will bring certain difficulties to the diagnosis. There are many reasons for negative TdT. The expression of TdT is different in different differentiation stages of lymphocytes, and the sensitivity of different detection methods and the false negative of TdT can be seen occasionally. In addition, it has been reported that the clinical characteristics and prognosis of TdT-negative- and TdT-positive-LBL/ALL are different. Understanding the significance of TdT expression, the causes of negative TdT, and the different characteristics of TdT-negative- and TdT-positive-LBL/ALL are helpful for clinical diagnosis, treatment selection and prognosis judgment. In this paper, relevant literature at home and abroad is reviewed, and the causes of negative TdT, the clinical characteristics, diagnosis and prognosis of TdT-negative-LBL/ALL were reviewed.
HOU Shumin, SHAO Jingbo. Research progress in clinical characteristics, diagnosis and prognosis of TdT-negative lymphoblastic lymphoma/acute lymphoblastic leukemia. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(1): 120-124 doi:10.3969/j.issn.1674-8115.2023.01.016
HOU Shumin was responsible for proposing writing ideas, collecting literatures and writing the review. SHAO Jingbo was responsible for checking and correcting the content of the review. Both authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
Both authors disclose no relevant conflict of interests.
CAO S, ZHOU L W, FENG Y. Research progress of TdT and its expression[J]. Chinese Journal of Clinical and Experimental Pathology, 2020, 36(10): 1190-1193.
WANG Y Y. Terminal deoxynucleotide transferase and alkaline phosphatase were detected by fluorescence enhanced assay[D]. Guangzhou: Jinan University, 2019.
ROSENBERG C A, BILL M, MAGUIRE O, et al. Imaging flow cytometry reveals a subset of TdT negative T-ALL blasts with very low forward scatter on conventional flow cytometry[J]. Cytometry B Clin Cytom, 2022, 102(2): 107-114.
WANG H J, SONG C H, GUREL Z, et al. Protein phosphatase 1 (PP1) and casein kinase Ⅱ (CK2) regulate Ikaros-mediated repression of TdT in thymocytes and T-cell leukemia[J]. Pediatr Blood Cancer, 2014, 61(12): 2230-2235.
CHEN Y Q, ZHAI X W, CHEN L. Study progress of T-lymphoblastic lymphoma in children[J]. Chinese Journal of Applied Clinical Pediatrics, 2019, 34(1): 68-72.
ARBER D A, ORAZI A, HASSERJIAN R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405.
LAI W P, TAN H. Current research status of diagnosis, treatment and prognostic factors of T-lymphoblastic lymphoma[J]. International Journal of Blood Transfusion and Hematology, 2019, 42(4): 332-337.
BILOUS N I, ABRAMENKO I V, CHUMAK A A, et al. NOTCH1 mutations in chronic lymphocytic leukemia patients sufferers of Chornobyl NPP accident[J]. Probl Radiac Med Radiobiol, 2015, 20: 319-327.
FIELDING A K, BANERJEE L, MARKS D I. Recent developments in the management of T-cell precursor acute lymphoblastic leukemia/lymphoma[J]. Curr Hematol Malig Rep, 2012, 7(2): 160-169.
LEI J Y, CHEN L, WANG Y, et al. Terminal deoxynucleotidyl transferase-negative lymphoblastic lymphoma/leukemia: a clinicopathological analysis of three cases[J]. Chinese Journal of Diagnostic Pathology, 2020, 27(8): 556-559.
BHAKER P, DAS A, RAJWANSHI A, et al. Precursor T-lymphoblastic lymphoma: speedy diagnosis in FNA and effusion cytology by morphology, immunochemistry, and flow cytometry[J]. Cancer Cytopathol, 2015, 123(9): 557-565.
ZHOU Y, FAN X S, ROUTBORT M, et al. Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma[J]. Mod Pathol, 2013, 26(10): 1338-1345.
HASSAN M, ABDULLAH H M A, WAHID A, et al. Terminal deoxynucleotidyl transferase (TdT)-negative T-cell lymphoblastic lymphoma with loss of the T-cell lineage-specific marker CD3 at relapse: a rare entity with an aggressive outcome[J]. BMJ Case Rep, 2018, 2018: bcr2018224570.
ROSHAL M, FROMM J R, WINTER S, et al. Immaturity associated antigens are lost during induction for T-cell lymphoblastic leukemia: implications for minimal residual disease detection[J]. Cytometry B Clin Cytom, 2010, 78(3): 139-146.
KLAIRMONT M M, ZHOU Y M, CHENG C, et al. Clinicopathologic and prognostic features of TdT-negative pediatric B-lymphoblastic leukemia[J]. Mod Pathol, 2021, 34(11): 2050-2054.
SABURI M, OGATA M, SATOU T, et al. Prognostic implications of TdT expression in acute myeloid leukemia with an intermediate-risk karyotype[J]. Int J Hematol, 2020, 112(1): 17-23.
DE BELLIS E, OTTONE T, MERCANTE L, et al. Terminal deoxynucleotidyl transferase (TdT) expression is associated with FLT3-ITD mutations in acute myeloid leukemia[J]. Leuk Res, 2020, 99: 106462.
