HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.
Exp Hematol
; 93: 38-43.e5, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33069783
ABSTRACT
Infant t(4;11) acute lymphoblastic leukemia is the most common leukemia in infant patients and has a highly aggressive nature. The patients have a dismal prognosis, which has not improved in more than a decade, suggesting that a better understanding of this disease is required. In the study described here, we analyzed two previously published RNA-sequencing data sets and gained further insights into the global transcriptomes of two known subgroups of this disease, which are characterized by the presence or absence of a homeobox gene expression signature. Specifically, we identified a remarkable mutually exclusive expression of the HOXA9/HOXA10 and IRX1 genes and termed the two subgroups iALL-HOXA9 and iALL-IRX1. This expression pattern is critical as it suggests that there is a fundamental difference between the two subgroups. Investigation of the transcriptomes of the two subgroups reveals a more aggressive nature for the iALL-IRX1 group, which is further supported by the fact that patients within this group have a worse prognosis and are also diagnosed at a younger age. This could be reflective of a developmentally earlier cell of origin for iALL-IRX1. Our analysis further uncovered critical differences between the two groups that may have an impact on treatment strategies. In summary, after a detailed investigation into the transcriptional profiles of iALL-HOXA9 and iALL-IRX1 patients, we highlight the importance of acknowledging that these two subgroups are different and that this is of clinical importance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Regulação Leucêmica da Expressão Gênica
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Proteínas de Fusão Oncogênica
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Proteínas de Homeodomínio
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Proteína de Leucina Linfoide-Mieloide
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Child
/
Humans
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Infant
Idioma:
En
Revista:
Exp Hematol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido