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4323 MPO and Trh within Leukemia Stem Cells Increased Chemosensitivity in Acute Myeloid Leukemia: A Single-Cell RNA Sequencing Approach

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster III
Hematology Disease Topics & Pathways:
Research, Translational Research
Monday, December 11, 2023, 6:00 PM-8:00 PM

Chieh-Lin Jerry Teng, PhD1*, Chung-Hsing Chen2*, Tzu‐Hung Hsiao3*, Ting-Shuan Wu3* and Yu-Min Liao, MD4

1Taichung Veterans General Hospital, Taichung, None, TWN
2National Institute of Cancer Research, National Health Research Institutes, Taiwan, Zhunan, Taiwan
3Taichung Veterans General Hospital, Taichung, Taiwan
4China Medical Univ. Hosp. Dept. of Medicine, Taichung, Taichung (city), TWN


The "7+3" regimen is widely recognized as the established standard induction therapy for newly diagnosed acute myeloid leukemia (AML), exhibiting a complete remission (CR) rate of 70%. However, the prognosis for patients who do not achieve CR following induction remains discouraging. Leukemia stem cells (LSCs) are recognized as major contributors to chemoresistance in AML. Hence, it is crucial to identify potential targets within LSCs that can overcome chemoresistance.

Patients and methods

This prospective study involved 20 consecutive de novo AML patients who underwent "7+3" induction therapy. These patients were divided into CR (n=15) and non-CR (n=5) groups. By employing single-cell RNA sequencing (scRNA-seq), we meticulously examined the cellular states of bone marrow mononuclear cells from AML patients at the time of diagnosis and identified LSCs among these cells. The genetic profiles of the LSCs were subsequently compared between the CR and non-CR groups and further validated using independent cohorts.


The non-CR AML patients exhibited a significant increase in the proportion of immature cells during hematopoiesis within the AML cell populations. Moreover, we found that expressions of MPO and TRH within LSCs were significantly higher in the CR than non-CR groups, which were further validated by independent cohorts. Furthermore, patients with higher expression of TRH and MPO demonstrated substantially improved relapse-free survival (p = 0.009 for TRH; p = 0.002 for MPO) and overall survival (p < 0.001 for TRH; p = 0.002 for MPO). The dysregulation of the OXPHOS pathway, along with altered interferon alpha and gamma responses, disrupted cholesterol homeostasis, and aberrant MYC activity, may contribute as underlying mechanisms for the observed association between MPO or TRH and chemotherapy response.


MPO and TRH in LSCs may increase chemosensitivity in AML and serve as chemoresponse biomarkers, offering potential benefits in guiding induction strategies for newly diagnosed AML patients

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH