未成熟急性白血病中 V(D)J 重排的分子特征

IF 2.1 4区 医学 Q3 HEMATOLOGY Leukemia research Pub Date : 2024-08-01 DOI:10.1016/j.leukres.2024.107521
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引用次数: 0

摘要

早期T细胞前体急性淋巴细胞白血病(ETP-ALL)、T淋巴细胞/髓细胞混合表型急性白血病(T/M-MPAL)和最小分化急性髓细胞白血病(AML-M0)都是未成熟急性白血病(AL),它们在不同程度上呈现出重叠的T细胞淋巴细胞和髓细胞特征,对疾病分类产生影响。V(D)J 基因片段重组分析是评估淋巴细胞系承诺和成熟度的一种有趣策略,可用于研究未成熟急性白血病中的白血病细胞。在此,我们重新研究了19例ETP-ALL、8例T/M-MPAL和12例AML-M0儿科患者,以确定与其他体细胞改变相关的V(D)J基因重排(V(D)J-r)特征。在ETP-ALL、T/M-MPAL和AML-M0中,分别有74%、25%和25%的患者发现了V(D)J-r。46%的ETP-ALL携带≥3个V(D)J-r,而在AML-M0和T/M-MPAL中,每个患者的V(D)J-r不超过一个。TCRD是ETPALL中重排最多的位点,但在其他AL中没有重排。在ETP-ALL中,N/KRAS突变与V(D)J-r缺失有关,而NF1缺失在V(D)J-r≥3的患者中最为常见。复发和死亡主要发生在携带一个或没有重排基因位点的患者中。与T/M-MPAL和AML-M0相比,我们队列中V(D)J-r的分子特征显示了ETP-ALL的独特特征。我们的研究结果还表明,ETP-ALL 患者的临床预后可能会受到囊泡细胞成熟度的影响,而囊泡细胞成熟度是通过重排 TCR 基因座的数量推断出来的。
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Molecular characterization of V(D)J rearrangements in immature acute leukemias

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.

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来源期刊
Leukemia research
Leukemia research 医学-血液学
CiteScore
4.00
自引率
3.70%
发文量
259
审稿时长
1 months
期刊介绍: Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.
期刊最新文献
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