Department of Immunology, Hospital Universitario Virgen del Rocío, Seville, Spain.
Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
Eur J Haematol. 2018 May;100(5):436-443. doi: 10.1111/ejh.13037. Epub 2018 Mar 1.
MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML).
Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed.
MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT.
We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.
MLL 基因参与了 80 多种已知的急性白血病基因融合。为了研究 MLL 伙伴基因和选定基因表达的相关性,在这项工作中,我们研究了 20 例 MLL 重排的急性髓系白血病(AML)患者。
本研究纳入了 20 例 MLL 重排 AML 患者和 138 例 AML 患者作为对照组。通过 RT-PCR 和测序,对 MLL 基因融合进行了特征分析,并对 EVI1、MEIS1、MLL-3'、RUNX1、SETBP1、HOXA5 和 FLT3 基因进行了相对基因表达定量。在接受治疗的背景下,对 MLL 遗传伙伴和基因表达与总生存的风险分层和相关性进行了评估。
MLLr 组的 OS 更类似于中危 AML。MLL 基因伙伴的类型与异体造血干细胞移植(allo-HSCT)反应有关;有 MLLT1 和 MLLT3,从中获益更好。接受 allo-HSCT 的患者中,MLL-3'区域、EVI1 和 FLT3 的表达与 OS 相关。
我们表明,MLL 基因伙伴可能对 allo-HSCT 反应有影响,我们提出了三个基因,其表达可能对接受 allo-HSCT 的患者的这种白血病的预后有用:MLL 的 3'区域、EVI1 和 FLT3。