Abstract A044: hTid-1 (DNAJA3) in tumorigenesis: A potential regulator of lymphoma pathobiology and therapeutic target

Abstract Background: Tumorous imaginal disc 1 (hTid-1/DNAJA3) is a mitochondrial co-chaperone of the Hsp40 family that regulates protein folding, degradation, and cellular stress responses via interaction with Hsp70. It plays a crucial role in key cellular processes, including apoptosis, proliferation, autophagy, and signal transduction. Dysregulation of these processes is central to the pathogenesis of haematological malignancies, including lymphoma. Objective: To comprehensively analyze the role of hTid-1 in cancer-related cellular pathways and highlight its potential relevance in lymphoma biology and targeted therapeutics. Methods: A detailed literature-based review was conducted to evaluate the structural variants, molecular interactions, and functional roles of hTid-1. Emphasis was placed on its involvement in oncogenic signaling pathways, protein quality control mechanisms, and mitochondrial homeostasis. Results: hTid-1 exists in two main splice variants, hTid-1L and hTid-1S, which exhibit opposing roles in apoptosis regulation. Functionally, hTid-1 acts as: A co-chaperone, modulating Hsp70 activity and cellular stress responses An E3 ubiquitin ligase, promoting degradation of oncogenic proteins such as EGFR and ErbB2 A regulator of autophagy, facilitating LC3-mediated autophagosome formation Additionally, hTid-1 influences major signaling pathways including JAK-STAT, Wnt/β-catenin, and NF-κB, which are critically involved in lymphoma progression, immune regulation, and cell survival. Altered expression of hTid-1 has been associated with tumor progression, metastasis, and poor prognosis in various cancers. Conclusion: hTid-1 emerges as a multifunctional regulator of cellular homeostasis and oncogenic signaling. Its involvement in apoptosis, proteostasis, and key cancer-associated pathways suggests a significant, yet underexplored, role in lymphoma pathobiology. Targeting hTid-1 and its interacting networks may provide novel therapeutic opportunities in lymphoma management. Citation Format: Anu Singh. hTid-1 (DNAJA3) in tumorigenesis: A potential regulator of lymphoma pathobiology and therapeutic target [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A044.