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

• Published in: Journal of genetics 2024-04, Vol.103 (1), Article 17
• Main Authors: BORRAYO-LÓPEZ, FRANCISCO JAVIER, IBARRA-CORTÉS, BERTHA, PEREA-DÍAZ, FRANCISCO JAVIER, MUÑOZ-ZÚÑIGA, ABRIL IXCHEL, MONTOYA-FUENTES, HÉCTOR, SOTO-PADILLA, JANETH MARGARITA, RIZO-DE LA TORRE, LOURDES DEL CARMEN
• Format: Article
• Language: English
• Subjects: Adolescent; Animal Genetics and Genomics; Biomedical and Life Sciences; Carrier Proteins - genetics; Child; Child, Preschool; Evolutionary Biology; Female; Fetal Hemoglobin - genetics; gamma-Globins - genetics; Genotype; GTP-Binding Proteins; Humans; Infant; Life Sciences; Male; Microbial Genetics and Genomics; Nuclear Proteins - genetics; Plant Genetics and Genomics; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Prognosis; Proto-Oncogene Proteins c-myb - genetics; Repressor Proteins - genetics; Research Article
• ISSN: 0973-7731; 0973-7731
• DOI: 10.1007/s12041-024-01470-0

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.