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

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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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Acknowledgements

We thank the haematology residents who helped in enrolling patients and collecting samples and the Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT) for granting a scholarship to the first author of this paper.

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Authors and Affiliations

  1. División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico

    FRANCISCO JAVIER BORRAYO-LÓPEZ, ABRIL IXCHEL MUÑOZ-ZÚÑIGA & LOURDES DEL CARMEN RIZO-DE LA TORRE

  2. Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG), Guadalajara, Jalisco, Mexico

    FRANCISCO JAVIER BORRAYO-LÓPEZ

  3. División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico

    FRANCISCO JAVIER BORRAYO-LÓPEZ & FRANCISCO JAVIER PEREA-DÍAZ

  4. Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud (CUCS), Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Universidad de Guadalajara (UDG), Guadalajara, Jalisco, Mexico

    BERTHA IBARRA-CORTÉS

  5. Licenciatura en Ingeniería en Biotecnología, Instituto Tecnológico y de Estudios Superiores de Occidente, San Pedro Tlaquepaque, Jalisco, Mexico

    ABRIL IXCHEL MUÑOZ-ZÚÑIGA

  6. Laboratorio de Microbiología Molecular, División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico

    HÉCTOR MONTOYA-FUENTES

  7. Departamento de Hematología Pediátrica, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México

    JANETH MARGARITA SOTO-PADILLA

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  1. FRANCISCO JAVIER BORRAYO-LÓPEZ
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Correspondence to LOURDES DEL CARMEN RIZO-DE LA TORRE.

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BORRAYO-LÓPEZ, F.J., IBARRA-CORTÉS, B., PEREA-DÍAZ, F.J. et al. Foetal haemoglobin elevation, unfavourable prognosis, and protective role of genetic variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 in children with ALL. J Genet 103, 17 (2024). https://doi.org/10.1007/s12041-024-01470-0

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