Prospective Study of CLL1 and CD45RA As Biomarkers of Leukemic Stem Cells to Predict Therapeutic Response in Acute Myeloid Leukemia

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.6105-6105
• Main Authors: Verghese, Andrea Verghese, Raju, Suguna, Li, Luke, Alfano, Jessica, Vacchi-Suzzi, Caterina, Lee, Christina Y., Lin, Hong, Liu, Suhu
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-206430

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal expansion of immature myeloblasts from leukemic stem cells (LSCs) and the disruption of normal hematopoiesis by hematopoietic stem cells (HSCs). Currently, treatment response is evaluated at the end of induction therapy (Days 28 ± 7). Despite an overall remission rate of about 70% for newly diagnosed AML and 30-50% for relapsed/refractory AML, many patients endure toxic treatments without clinical benefit. There is a need for biomarkers that enable timely evaluation of treatment response and facilitate real-time therapy adjustments that optimize therapeutic benefit while minimizing unnecessary toxicity. Our prior retrospective study at Stony Brook University Hospital (SBUH) evaluated the dynamic changes of LSC versus HSC in AML patients using flow cytometric markers. Among the five LSC markers studied, changes in LSC/HSC subsets identified by CLL1 and CD45RA showed the strongest correlation with treatment response. Moreover, the presence of CLL1+ or CD45RA+ LSC/HSC subsets in peripheral blood correlated highly with bone marrow aspirate findings, suggesting that peripheral blood monitoring of LSC/HSC subsets could be a timely, non-invasive method to track LSC/HSC dynamics during AML treatment. Aims: The primary aims of this study are to assess: 1) the feasibility of tracking changes in LSC/HSC subsets using peripheral blood CLL1 and CD45RA as biomarkers on Days 3, 5, and 7 of induction therapy in AML patients, and 2) the feasibility of using LSC/HSC subsets to predict therapeutic response as evaluated by bone marrow examination at the end of induction cycle (Days 28 ± 7). Methods: This pilot prospective study plans to recruit 20 AML patients from SBUH who are 18 years or older, with newly diagnosed or relapsed/refractory AML and pre-treatment LSC marker (CLL1 and/or CD45RA) expression ≥50% of total HSCs. Following informed consent, peripheral blood samples are collected and processed for multicolor flow cytometry (MFC) on Days 3, 5, and 7 of induction therapy. The HSC population is defined as CD45dim/SSC and CD34+CD38low/-. CLL1 or CD45RA positive HSCs are identified as LSCs. LSC/HSC subsets are calculated as the percentage of CLL1+ or CD45RA+ cells within the HSC population. Changes in LSC/HSC subsets from pre-treatment will be evaluated and compared between patients with persistent disease and those achieving complete remission after induction chem