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CC BY 4.0 · Indian J Med Paediatr Oncol
DOI: 10.1055/s-0045-1809173
Brief Communication

Terminal Deoxynucleotidyl Transferase (TdT) Positive Acute Myeloid Leukemia with C-MYC and BCL2 Expression: A Distinct Biological Entity with Potential Clinical Implications

Chinmayee Panigrahi
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Biswajit Bhuyan 
2   Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
3   Department of Clinical Hematology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Prabodha Kumar Das
2   Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Somanath Padhi 
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Gaurav Chhabra 
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Ashutosh Panigrahi 
2   Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Arushi Choudhary
4   Department of General Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Saheeta Sudarsini
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Prapti Acharya
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Debasis Jash
1   Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
› Author Affiliations Funding None.
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Abstract

Terminal deoxynucleotidyl transferase (TdT) is a unique deoxyribonucleic acid polymerase whose overexpression has been used as an important biomarker in the diagnosis of precursor B or T cell acute lymphoblastic leukemia/lymphoma. Over the last few years, TdT has been increasingly implicated in the genesis of mutant Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and NPM1 isoforms, two key events in the myeloid stem cell leukemogenesis. This article studies the diagnostic and prognostic implications of immunoexpression of TdT, C-MYC, and BCL2 in acute myeloid leukemia (AML). We retrospectively reviewed seven cases of TdT positive (+), myeloperoxidase negative AMLs (2022–2024) with C-MYC and/or BCL2 expression by immunohistochemistry (IHC), and correlated these with flow cytometric (FC), molecular, and/or cytogenetics data (wherever available) along with outcome following induction chemotherapy. Morphologically, all these cases resembled French-American-British M0, M1, and M5 AMLs, or even high-grade lymphoproliferative neoplasms with moderate to stronger nuclear positivity for TdT and C-MYC in a higher proportion neoplastic cell along with stronger cytoplasmic BCL2 expression. Two were FLT3-ITD mutated, one was TP53 mutated, one had high-risk cytogenetics, whereas the remainder had no detectable abnormalities on molecular testing with variable degree of therapeutic response. Literature review highlighted the negative impact of overall, event-free, and relapse-free survivals among TdT and C-MYC positive AMLs whereas BCL2 expressors were likely to have increased chemoresistance. We suggest that TdT +/C-MYC +/BCL2+ AMLs may serve as distinct biological subtype; and IHC/FC-based testing should be a part of routine diagnostic workup for better risk stratification in AMLs.

Keywords

immunohistochemistry - TdT - myeloid leukemia - molecular testing - prognosis

Authors' Contributions

C.P. and S.P.: Conceptual design, data curation, diagnosis, writing the original draft, review, and editing. B.B., P.K.D., and A.P.: Management of cases, follow-up data, and critical review of scientific content. G.C., S.P., and D.J.: Flow cytometry evaluation of cases. S.S. and P.A.: Diagnosis and literature review. A.C.: Literature review.


Ethics Approval

The study was part of the retrospective review proposal approved by the Institutional Ethics Committee of AIIMS, Bhubaneswar (T/IM-NF/Patho/24/52).


Patient's Consent

Patient consent is not required.




Publication History

Article published online:
19 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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