CD74 is expressed in a subset of pediatric acute myeloid leukemia patients and is a promising target for therapy: a report from the Children’s Oncology Group

• 發表在: Haematologica
• Main Authors: Andrew J. Menssen, Chad A. Hudson, Todd Alonzo, Robert Gerbing, Laura Pardo, Amanda Leonti, Jacqueline A. Cook, Fan-Chi Hsu, Loren L. Lott, Fangyan Dai, Collette Fearing, Keely Ghirardelli, Tiffany Hylkema, Katherine Tarlock, Keith R. Loeb, Edward A. Kolb, Todd Cooper, Jessica Pollard, Denise A. Wells, Michael R. Loken, Richard Aplenc, Soheil Meshinchi, Lisa Eidenschink Brodersen
• 格式: Article
• 語言: 英语
• 出版: Ferrata Storti Foundation 2024-02-01
• 在線閱讀: https://haematologica.org/article/view/11426

As curative therapies for pediatric AML remain elusive, identifying potential new treatment targets is vital. We assessed the cell surface expression of CD74, also known as the MHC-II invariant chain, by multidimensional flow cytometry in 973 patients enrolled in the Children’s Oncology Group AAML1031 clinical trial. 38% of pediatric AML patients expressed CD74 at any level and a comparison to normal hematopoietic cells revealed a subset with increased expression relative to normal myeloid progenitor cells. Pediatric AML patients expressing high intensity CD74 typically had an immature immunophenotype and an increased frequency of lymphoid antigen expression. Increased CD74 expression was associated with older patients with lower WBC and peripheral blood blast counts, and was enriched for t(8;21), trisomy 8, and CEBPA mutations. Overall, high CD74 expression was associated with low-risk status, however 26% of patients were allocated to high-risk protocol status and 5-year event free survival was 53%, indicating that a significant number of high expressing patients had poor outcomes. In vitro pre-clinical studies indicate that anti-CD74 therapy demonstrates efficacy against AML cells but has little impact on normal CD34+ cells. Together, we demonstrate that CD74 is expressed on a subset of pediatric AMLs at increased levels compared to normal hematopoietic cells and is a promising target for therapy in expressing patients. Given that nearly half of patients expressing CD74 at high levels experience an adverse event within 5 years, and the availability of CD74 targeting drugs, this represents a promising line of therapy worthy of additional investigation.