Abstract：
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL), T-Lymphoid/Myeloid Mixed Phenotype Acute Leukemia (T/M-MPAL), and Acute Myeloid Leukemia with minimal differentiation (AML-M0) are immature acute leukemias (AL) that present overlapping T-cell lymphoid and myeloid features at different degrees, with impact to disease classification. An interesting strategy to assess lymphoid lineage commitment and maturation is the analysis of V(D)J gene segment recombination, which can be applied to investigate leukemic cells in immature AL. Herein, we revisited 19 ETP-ALL, 8 T/M-MPAL, and 12 AML-M0 pediatric patients to characterize V(D)J rearrangement (V(D)J-r) profiles associated with other somatic alterations. V(D)J-r were identified in 74 %, 25 %, and 25 % of ETP-ALL, T/M-MPAL, and AML-M0, respectively. Forty-six percent of ETP-ALL harbored ≥ 3 V(D)J-r, while there was no more than one V(D)J-r per patient in AML-M0 and T/M-MPAL. TCRD was the most rearranged locus in ETPALL, but it was not rearranged in other AL. In ETP-ALL, N/KRAS mutations were associated with absence of V(D)J-r, while NF1 deletion was most frequent in patients with ≥ 3 V(D)J-r. Relapse and death occurred mainly in patients harboring one or no rearranged locus. Molecular characterization of V(D)J-r in our cohort indicates a distinct profile of ETP-ALL, compared to T/M-MPAL and AML-M0. Our findings also suggest that the clinical outcome of ETP-ALL patients may be affected by blast cell maturity, inferred from the number of rearranged TCR loci.
摘要：
早期T细胞前体急性淋巴细胞白血病（ETP-ALL），T-淋巴/髓系混合表型急性白血病(T/M-MPAL),急性髓系白血病（AML-M0）是未成熟的急性白血病（AL），在不同程度上呈现重叠的T细胞淋巴样和髓样特征，对疾病分类有影响。评估淋巴谱系定型和成熟的一个有趣的策略是分析V（D）J基因片段重组，可用于研究未成熟AL中的白血病细胞。在这里，我们重访了19个ETP-ALL，8T/M-MPAL,和12名AML-M0儿科患者表征与其他体细胞改变相关的V（D）J重排（V（D）J-r）谱。V(D)J-r的比例为74%，25%,和25%的ETP-ALL，T/M-MPAL,和AML-M0。46%的ETP-ALL藏有≥3V(D)J-r，而AML-M0和T/M-MPAL中每个患者的V（D）J-r不超过一个。TCRD是ETPALL中重排最多的基因座，但它没有在其他AL重新排列。在ETP-ALL中,N/KRAS突变与V(D)J-r缺失相关,而NF1缺失在≥3V（D）J-r的患者中最常见。复发和死亡主要发生在有一个或没有重排基因座的患者中。我们队列中V（D）J-r的分子特征表明ETP-ALL的独特特征，与T/M-MPAL和AML-M0相比。我们的研究结果还表明，ETP-ALL患者的临床结局可能受到母细胞成熟度的影响。从重排的TCR基因座的数量推断。
