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Infant t(4;11) acute lymphoblastic leukemia is the most common leukemia found 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 better understanding of this disease is required. In this study we analyze two previously published RNA sequencing datasets and gain further insights into the global transcriptome of two known sub-groups of this disease, which are characterized by the presence or absence of a homeobox gene expression signature. Specifically, we identify a remarkable mutually exclusive expression of the HOXA9/HOXA10 and IRX1 genes and have thus termed the two sub-groups iALL-HOXA9 and iALL-IRX1. This expression pattern is of critical importance as it suggests that there is a fundamental difference between the two sub-groups. Investigation of the transcriptome of the two sub-groups reveals a more aggressive nature of 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 uncovers critical differences between the two groups that may impact on treatment strategies for the two groups. In summary, through a detailed investigation into the transcriptional profile of iALL-HOXA9 and iALL-IRX1 patients, we highlight the importance of acknowledging that these two sub-groups are different, and that this is of clinical importance.
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10.1016/j.exphem.2020.10.002
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HOXA9/IRX1 expression pattern defines two sub-groups of infant MLL-AF4-driven Acute Lymphoblastic Leukemia.
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