Department of Pathology, Kurume University School of medicine, Kurume, Fukuoka, Japan.
Department of Orthopedic surgery, Kurume University School of medicine, Kurume, Fukuoka, Japan.
Int J Lab Hematol. 2020 Dec;42(6):842-848. doi: 10.1111/ijlh.13289. Epub 2020 Aug 3.
Adult T-cell leukemia/lymphoma (ATLL) is a malignant peripheral T-cell neoplasm associated with human T-cell leukemia virus type-1 (HTLV-1). The acute and lymphoma subtypes are regarded as aggressive ATLLs, and the overall survival (OS) of patients remains poor. Transforming acidic coiled-coil-containing protein 3 (TACC3) regulates microtubules, which are associated with cancer-related proteins overexpressed in various cancers. Such a relationship has not been reported in hematopoietic tumors, including ATLL.
We examined tissue microarrays of histological samples from 92 cases of aggressive ATLL and assessed clinical features, including TACC3 protein expression levels.
Compared with TACC3-low, TACC3-high ATLL patients were significantly older (P < .001), with a tendency toward pleomorphic variant over other morphological classifications (P = .019). TACC3-high patients (median survival time [MST] 10.6 months, confidence interval [CI] [6.27-15.6]) had poorer OS compared to TACC3-low patients (MST 20 months, CI [9.43-38.5]) (P = .0168). Moreover, multivariate analysis on TACC3 expression levels suggests that TACC3-high is an independent significant prognostic factor (HR, 1.700; 95% CI, 1.037-2.753; P = .0355).
Certain drugs that inhibit TACC3-overexpressing neoplastic cells are used clinically. Further studies might highlight a key role for TACC3 in the oncogenesis and progression of ATLL.
成人 T 细胞白血病/淋巴瘤(ATLL)是一种与人类 T 细胞白血病病毒 1 型(HTLV-1)相关的恶性外周 T 细胞肿瘤。急性和淋巴瘤亚型被认为是侵袭性 ATLL,患者的总体生存率(OS)仍然较差。转化酸性卷曲螺旋蛋白 3(TACC3)调节微管,与各种癌症中过度表达的癌症相关蛋白有关。这种关系尚未在包括 ATLL 在内的造血肿瘤中报道。
我们检查了 92 例侵袭性 ATLL 组织学样本的组织微阵列,并评估了临床特征,包括 TACC3 蛋白表达水平。
与 TACC3 低相比,TACC3 高的 ATLL 患者年龄明显较大(P<0.001),与其他形态学分型相比,多形性变异的趋势更为明显(P=0.019)。TACC3 高患者(中位生存时间 [MST] 10.6 个月,置信区间 [CI] [6.27-15.6])的 OS 明显低于 TACC3 低患者(MST 20 个月,CI [9.43-38.5])(P=0.0168)。此外,对 TACC3 表达水平的多变量分析表明,TACC3 高是独立的显著预后因素(HR,1.700;95%CI,1.037-2.753;P=0.0355)。
某些抑制 TACC3 过表达肿瘤细胞的药物在临床上已被应用。进一步的研究可能会突出 TACC3 在 ATLL 发生和进展中的关键作用。