Veltri Giulia, Lovisa Federica, Cortese Giuliana, Pillon Marta, Carraro Elisa, Cesaro Simone, Provenzi Massimo, Buffardi Salvatore, Francescato Samuela, Biffi Alessandra, Buldini Barbara, Conter Valentino, Serafin Valentina, Mussolin Lara
Maternal and Child Health Department, University of Padova, Padova, Italy.
Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.
Front Oncol. 2022 Jul 8;12:913487. doi: 10.3389/fonc.2022.913487. eCollection 2022.
T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) arise from the transformation of precursor T-cells sharing common morphological and immunophenotypic features. Despite this, T-LBL and T-ALL show different genomic/transcriptomic profiles and whether they represent two distinct disease entities or variant manifestations of the same disease is still a matter of debate. In this work, we performed a Reverse Phase Protein Array study on T-LBL and T-ALL samples and demonstrated that they are characterized by a different phosphoproteomic profile. Indeed, T-LBLs showed the hyperactivation of FAK/ERK1/2 and AKT/mTOR pathways, whereas JAK/STAT pathway was significantly hyperphosphorylated in T-ALLs. Moreover, since the only criteria for discriminating T-LBL from T-ALL is blasts' infiltration below 25% in the bone marrow and lymphoma patients can present with a percentage of blasts close to this cut-off, a biomarker that could help distinguishing the two diseases would be of great help for the clinical diagnosis and treatment decision. Pursuing this aim, we identified a proteomic signature of six proteins whose expression/activation was able to discriminate stage IV T-LBL from T-ALL. Moreover, we demonstrated that AKT hyperphosphorylation alone was able to distinguish stage IV T-LBL from both T-ALL and stage III T-LBL. Concluding, these data demonstrate that T-ALL and T-LBL bear different phosphoproteomic profiles, further sustaining the hypothesis of the two disease as different entities and paving the way for the identification of new biomarkers able to distinguish stage IV T-LBL from T-ALL disease, so far based only on BM involvement criteria.
T 细胞淋巴母细胞淋巴瘤（T-LBL）和淋巴母细胞白血病（T-ALL）起源于具有共同形态学和免疫表型特征的前体 T 细胞的转化。尽管如此，T-LBL 和 T-ALL 表现出不同的基因组/转录组谱，它们是代表两种不同的疾病实体还是同一疾病的不同表现形式仍存在争议。在这项工作中，我们对 T-LBL 和 T-ALL 样本进行了反向蛋白质阵列研究，并证明它们具有不同的磷酸化蛋白质组谱。事实上，T-LBL 显示 FAK/ERK1/2 和 AKT/mTOR 通路的过度激活，而 JAK/STAT 通路在 T-ALL 中显著过度磷酸化。此外，由于区分 T-LBL 和 T-ALL 的唯一标准是骨髓中原始细胞浸润低于 25%，且淋巴瘤患者的原始细胞百分比可能接近这个临界值，因此一种有助于区分这两种疾病的生物标志物将对临床诊断和治疗决策有很大帮助。为了实现这一目标，我们确定了一种由六种蛋白质组成的蛋白质组特征，其表达/激活能够区分 IV 期 T-LBL 和 T-ALL。此外，我们证明仅 AKT 过度磷酸化就能区分 IV 期 T-LBL 与 T-ALL 和 III 期 T-LBL。总之，这些数据表明 T-ALL 和 T-LBL 具有不同的磷酸化蛋白质组谱，进一步支持了这两种疾病是不同实体的假设，并为识别能够区分 IV 期 T-LBL 和 T-ALL 疾病的新生物标志物铺平了道路，目前这两种疾病仅基于骨髓受累标准来区分。
