T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.
T细胞急性淋巴细胞白血病(T-ALL)占儿童ALL的15%和成人ALL的25%。由于复发/难治性病例预后尤其不良，在诊断时识别预后因素对于调整高危患者的治疗方案至关重要。与急性髓系白血病和B细胞前体ALL不同，染色体易位产生具有显著预后影响的嵌合融合蛋白在T-ALL中报道较少。针对这一问题，研究者对连续522例成人和儿童T-ALL病例应用RT-MPLA检测，在20%的病例中发现了融合转录本。其中最常见的是PICALM-MLLT10（4%，23例）、NUP214-ABL1（3%，19例）和SET-NUP214（3%，18例）。为进一步明确融合转录本的预后价值，研究者对235例患者（包括GRAALL2003/05试验中的138例成人和FRALLE2000试验中的97例儿童）的临床生物学特征进行分析。结果显示，携带MLLT10、KMT2A和SET融合转录本的HOXA反式失调T-ALL患者（占235例中的17%，39例）预后较差，其5年无事件生存率为35.7%（对照组为63.7%，风险比=1.63；p=0.04），且累计复发率呈升高趋势（5年累计复发率=45.7% vs 25.2%，风险比=1.6；p=0.11）。研究表明，RT-MLPA可准确识别T-ALL融合转录本状态，有助于为高危患者制定风险适应性的治疗策略。
Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
肿瘤(癌症)患者之家