Buldini Barbara, Faggin Giovanni, Porcù Elena, Scarparo Pamela, Polato Katia, Tregnago Claudia, Varotto Elena, Rizzardi Paolo, Rizzari Carmelo, Locatelli Franco, Biffi Alessandra, Pigazzi Martina
Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Women's and Child Health Department, University of Padua, Padua, Italy.
Pediatric Hematology, Oncology, Hematopoietic Cell and Gene Therapy Reserach Area, Istituto di Ricerca Pediatrica (IRP) - Città della Speranza, Padua, Italy.
Cytometry A. 2023 Dec;103(12):1004-1009. doi: 10.1002/cyto.a.24790. Epub 2023 Oct 24.
In the development of novel immunotherapeutic approaches, the step of target identification is a challenging process, because it aims at identifying robust tumor-associated antigens (TAAs) specific for the pathological population and causing no off-target effects. Here we propose CD72 as a novel and robust TAA for pediatric acute leukemias. We provided an outline of CD72 expression assessed by flow cytometry on a variety of cancer cell lines and primary samples, including normal bone marrow (BM) samples and hematopoietic stem and progenitor cells. We analyzed CD 72 expression on a cohort of 495 pathological pediatric BM aspirates, including: 215 B-cell precursor acute lymphoblastic leukemias (BCP-ALL), 156 acute myeloid leukemias (AMLs), 88 T-lineage ALLs or lymphoblastic lymphomas with BM infiltration, 13 B-lineage lymphoblastic lymphomas with BM infiltration, 9 myelodysplastic syndromes with increased blasts (5%-9% blasts on BM: MDS-IB1) and 14 non-hematopoietic solid tumors infiltrating BM. Results showed that CD72 is highly expressed in almost all BCP-ALL and the majority of AML at diagnosis, including BCP-ALL cases characterized by CD19 loss. These findings support a potential role for advanced diagnostics and novel immunotherapy approaches, providing a pan-ALL and AML target.
在新型免疫治疗方法的研发过程中，靶点识别步骤是一个具有挑战性的过程，因为它旨在识别对病理人群具有特异性且不会产生脱靶效应的强大肿瘤相关抗原（TAA）。在此，我们提出CD72作为小儿急性白血病的一种新型且强大的TAA。我们概述了通过流式细胞术评估的CD72在多种癌细胞系和原代样本中的表达情况，这些样本包括正常骨髓（BM）样本以及造血干细胞和祖细胞。我们分析了495例小儿病理BM穿刺样本中CD72的表达情况，其中包括：215例B细胞前体急性淋巴细胞白血病（BCP-ALL）、156例急性髓系白血病（AML）、88例伴有BM浸润的T系ALL或淋巴母细胞淋巴瘤、13例伴有BM浸润的B系淋巴母细胞淋巴瘤、9例伴有原始细胞增多的骨髓增生异常综合征（BM中原始细胞占5%-9%：MDS-IB1）以及14例浸润BM的非造血实体瘤。结果显示，在诊断时，CD72在几乎所有BCP-ALL以及大多数AML中高表达，包括以CD19缺失为特征的BCP-ALL病例。这些发现支持了先进诊断和新型免疫治疗方法的潜在作用，提供了一个全ALL和AML靶点。
