Department of Pathology and Laboratory Medicine, Division of Hematopathology, University of Miami/Sylvester Comprehensive Cancer Center & Jackson Memorial Hospital, Miami, FL, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2022 Sep;35(9):1220-1226. doi: 10.1038/s41379-022-01063-1. Epub 2022 Mar 23.
T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 (15%) medullary type. LMO2 expression was present in 50 (74.6%) initial biopsies with an average of 87% positive tumor cells (range 30-100%). LMO2 expression in ETP, medullary and cortical T-LLs was not statistically different. In patients with biopsies after initial therapy, LMO2 expression was stable. LMO2 expression was associated with longer OS (p = 0.048) regardless of T-lymphoblast stage or other clinicopathologic features. These findings indicate that LMO2 is a promising new prognostic marker that could predict patients' outcomes and potentially be targeted for novel chemotherapy, i.e. PARP1/2 inhibitors, which have been shown to enhance chemotherapy sensitivity in LMO2 expressing diffuse large B cell lymphoma (DLBCL) tumors by decreasing DNA repair efficiency.
T 淋巴母细胞白血病/淋巴瘤（T-LL）是一种不成熟 T 细胞的侵袭性恶性肿瘤，总体生存率（OS）较差，需要新的治疗方法。LIM 结构域只有 2（LMO2）是造血细胞发育的关键调节剂，由于染色体异常，T-LL 中可能过度表达。失调的 LMO2 表达通过诱导 T 细胞分化阻滞和持续胸腺细胞自我更新，促进 T-LL 的发展。然而，LMO2 在 T-LL 中的表达及其生物学意义在很大程度上仍不清楚。我们分析了 67 例患者的 100 例初始和随访 T-LL 活检中的 LMO2 表达，包括 31 例（46%）早期前体细胞 T 细胞（ETP）-ALL、26 例（39%）皮质和 10 例（15%）髓质型。50 例（74.6%）初始活检中有 LMO2 表达，平均有 87%的肿瘤细胞阳性（范围 30-100%）。ETP、髓质和皮质 T-LL 中的 LMO2 表达无统计学差异。在初始治疗后进行活检的患者中，LMO2 表达稳定。LMO2 表达与较长的 OS 相关（p=0.048），无论 T 淋巴母细胞阶段或其他临床病理特征如何。这些发现表明，LMO2 是一种有前途的新预后标志物，可预测患者的结局，并可能成为新的化疗靶点，即 PARP1/2 抑制剂，已显示通过降低 DNA 修复效率，增强 LMO2 表达弥漫性大 B 细胞淋巴瘤（DLBCL）肿瘤对化疗的敏感性。
