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成人 Ph-阴性急性 T 淋巴细胞白血病中 7q34()和 9p21.3()的双等位基因缺失。

Biallelic Loss of 7q34 () and 9p21.3 (/) in Adult Ph-Negative Acute T-Lymphoblastic Leukemia.

机构信息

National Medical Research Center for Hematology, 125167 Moscow, Russia.

Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

出版信息

Int J Mol Sci. 2024 Sep 29;25(19):10482. doi: 10.3390/ijms251910482.

Abstract

Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph-negative T-ALL. Chromosomal microarray analysis (CMA) was performed for 47 patients with de novo Ph-negative T-ALL, who received treatment according to RALL-2016m clinical protocol at the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Out of forty-seven patients, only three had normal molecular karyotype. The other 44 patients had multiple gains, losses, and copy neutral losses of heterozygosity. Biallelic losses were found in 14 patients (30%). In ten patients (21%), a biallelic deletion of 9p21.3 involved a different number of genes, however gene loss was noted in all ten cases. For seven patients (15%), a biallelic deletion of 7q34 was found, including two genes-, located within the T-cell receptor beta () locus. A clonal rearrangement of the gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant ( = 0.01) and a trend for 7q34 ( = 0.12) being observed.

摘要

急性淋巴细胞白血病 (ALL) 的肿瘤细胞可能具有各种遗传异常。其中一些导致某些基因完全缺失。我们的目的是揭示 Ph-阴性 T-ALL 中基因的双等位基因缺失。对 2017 年至 2023 年在俄罗斯莫斯科国家血液学医学研究中心根据 RALL-2016m 临床方案接受治疗的 47 例新发 Ph-阴性 T-ALL 患者进行了染色体微阵列分析 (CMA)。在 47 例患者中,只有 3 例具有正常的分子核型。其他 44 例患者存在多种增益、缺失和杂合性丢失的拷贝中性。在 14 例患者(30%)中发现了双等位基因缺失。在 10 例患者(21%)中,9p21.3 的双等位基因缺失涉及不同数量的基因,但在所有 10 例中均发现了基因缺失。在 7 例患者(15%)中,发现了 7q34 的双等位基因缺失,包括两个基因- ,位于 T 细胞受体β()基因座内。在 7q34 双等位基因缺失的 6 例中,均发现了 基因的克隆重排。双等位基因缺失均可被视为有利的预后因素,与 9p21 具有统计学意义(=0.01),与 7q34 呈趋势(=0.12)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a13/11477120/c116438f560d/ijms-25-10482-g001.jpg

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