Foetal haemoglobin elevation, unfavourable prognosis, and protective role of genetic variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 in children with ALL

IF 2.9 4区生物学 Q1 EDUCATION & EDUCATIONAL RESEARCH Journal of Genetics Pub Date : 2024-04-17 DOI:10.1007/s12041-024-01470-0

FRANCISCO JAVIER BORRAYO-LÓPEZ, BERTHA IBARRA-CORTÉS, FRANCISCO JAVIER PEREA-DÍAZ, ABRIL IXCHEL MUÑOZ-ZÚÑIGA, HÉCTOR MONTOYA-FUENTES, JANETH MARGARITA SOTO-PADILLA, LOURDES DEL CARMEN RIZO-DE LA TORRE

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Abstract

In acute lymphoblastic leukaemia (ALL), elevated foetal haemoglobin (HbF) levels have been associated with the prognosis of patients. Genetic variants in HbF regulatory genes: BAF chromatin remodelling complex subunit (BCL11A), HBS1L-MYB transcriptional GTPase intergenic region (HBS1L-MYB), Krüppel-like factor 1 (KLF1), haemoglobin gamma subunit 2 (HBG2), haemoglobin gamma subunit 1 (HBG1), and haemoglobin subunit beta pseudogene 1 (HBBP1) are often associated with elevated HbF concentration. This study investigated the association of genetic variants in HbF regulatory genes with HbF concentration, unfavourable prognosis, and outcome in children with ALL. We quantified HbF concentration and genotyped 17 genetic variants in 48 patients with ALL and 64 children without ALL as a reference group. HbF concentration was higher in patients than in the reference group (4.4% vs 1.4%), and 75% (n = 36) of the patients had HbF > 2.5%. Unfavourable prognosis ALL was established in 68.8% (n = 33) of the patients. Variant HBG2 rs7482144 was associated with high HbF concentration (P = 0.015); while HBS1L-MYB rs9399137 (P = 0.001), HBG2 rs7482144 (P = 0.001) and the β-globin genes HBG2, HBG1, and HBPP1 haplotype TGC (P = 0.017) with unfavourable prognosis ALL. Additionally, variant BCL11A rs4671393 showed a protective role (P = 0.0001). In conclusion, variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 may play a significant role in ALL.

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胎儿血红蛋白升高、预后不良以及遗传变异 HBG2 rs7482144、HBS1L-MYB rs9399137 和 BCL11A rs4671393 在 ALL 儿童中的保护作用

在急性淋巴细胞白血病（ALL）中，胎儿血红蛋白（HbF）水平的升高与患者的预后有关。HbF 调控基因的遗传变异包括BAF染色质重塑复合物亚基（BCL11A）、HBS1L-MYB转录GTP酶基因间区（HBS1L-MYB）、Krüppel样因子1（KLF1）、血红蛋白γ亚基2（HBG2）、血红蛋白γ亚基1（HBG1）和血红蛋白亚基β伪基因1（HBBP1）的遗传变异往往与HbF浓度升高有关。本研究调查了HbF调控基因的遗传变异与HbF浓度、不利预后和ALL患儿预后的关系。我们对 48 名 ALL 患者和 64 名非 ALL 儿童（作为参照组）的 HbF 浓度进行了量化，并对 17 个遗传变异进行了基因分型。患者的 HbF 浓度高于参照组（4.4% 对 1.4%），75% 的患者（n = 36）的 HbF 为 2.5%。68.8%（33 人）的患者预后不良。变异型 HBG2 rs7482144 与高 HbF 浓度相关（P = 0.015）；而 HBS1L-MYB rs9399137（P = 0.001）、HBG2 rs7482144（P = 0.001）和β-球蛋白基因 HBG2、HBG1 和 HBPP1 单倍型 TGC（P = 0.017）与预后不良的 ALL 相关。此外，变体 BCL11A rs4671393 具有保护作用（P = 0.0001）。总之，变异体HBG2 rs7482144、HBS1L-MYB rs9399137和BCL11A rs4671393可能在ALL中发挥重要作用。

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来源期刊

Journal of Genetics 生物-遗传学

CiteScore

3.10

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The journal retains its traditional interest in evolutionary research that is of relevance to geneticists, even if this is not explicitly genetical in nature. The journal covers all areas of genetics and evolution,including molecular genetics and molecular evolution.It publishes papers and review articles on current topics, commentaries and essayson ideas and trends in genetics and evolutionary biology, historical developments, debates and book reviews. From 2010 onwards, the journal has published a special category of papers termed ‘Online Resources’. These are brief reports on the development and the routine use of molecular markers for assessing genetic variability within and among species. Also published are reports outlining pedagogical approaches in genetics teaching.