The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype

Abstract Deletions of 9q are recurring cytogenetic abnormalities in acute myeloid leukaemia (AML). In approximately one-third of cases del(9q) occurs in association with t(8;21). We have previously identified a 2.4Mb region located on 9q21.32–21.33 which is deleted in cases of del(9q) AML - the del(9q) commonly deleted region (CDR). This region encodes 11 genes which we have also previously shown not to be mutated in del(9q) AML. In order to further investigate the role of these genes in AML and in particular to elucidate the pathogenesis of del(9q) AML we have examined the expression of these genes in AML. RNA was extracted from the bone marrow or peripheral blood of patients with AML at the time of diagnosis. Patient samples from the following cytogenetic subgroups were included in this study: (1) del(9q) AML (n=8) - this includes 3 patients with associated t(8;21); (2) t(8;21) but no del(9q) (n=15); (3) Normal karyotype (n=6); (4) Complex Karyotype (n=6). Taqman assays were designed for 9 of the 11 genes located within the del(9q) CDR: FRMD3; ENSG00000148057; UBQLN1; GKAP42; Q9UF54; Q8N2B1; Q9H9A7; SLC28A3; NTRK2. For the other 2 genes within the region Taqman assays could not be performed because of uniformly low expression levels (Q8IZ41) and lack of specificity of primer-design (HNRPK). CD34-purified progenitors from normal individuals were used as controls. It was found that 6 of the 9 genes were significantly down-regulated in del(9q) AML (p<0.05): ENSG00000148057; UBQLN1; Q9UF54; Q8N2B1; Q9H9A7; NTRK2. Since del(9q) is commonly associated with t(8;21), cases of t(8;21) in which del(9q) was not present were also analysed for the expression levels of the del(9q) CDR genes. It was found that 5 of the 9 genes were significantly down regulated in t(8;21) AML (ENSG00000148057; Q9UF54; Q8N2B1; Q9H9A7; SLC28A3) (p<0.05). Only two of these genes were found to be down-regulated in AML of normal karyotype (Q9H9A7 and UBQLN1) (p<0.05) and no significant down-regulation was detected in any of these genes in AML of complex karyotype. Our findings indicate that several genes from within the del(9q) AML CDR are down-regulated in del(9q) AML. A similar pattern of down-regulation is found in cases of t(8;21) even in the absence of del(9q) AML. This suggests that down-regulation of one or more of these genes may be important in the pathogenesis of AML. It may therefore be hypothesized that this pattern of gene down-regulation provides a mechanism common to the development of AML with both del(9q) and t(8;21).

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The Role of Macrophages in Acute Myeloid Leukaemia Progression and Sensitivity to Chemotherapy

10.14264/098afb0 ◽

2021 ◽

Author(s):

◽

Thomas Keech

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Acute Myeloid

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Beneficial role of increased FOXP3+ regulatory T-cells in acute myeloid leukaemia therapy response

British Journal of Haematology ◽

10.1111/bjh.14819 ◽

2017 ◽

Vol 182 (4) ◽

pp. 581-583 ◽

Cited By ~ 3

Author(s):

Thomas Menter ◽

Boris Kuzmanic ◽

Christoph Bucher ◽

Michael Medinger ◽

Joerg Halter ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Therapy Response ◽

Beneficial Role ◽

Leukaemia Therapy ◽

Acute Myeloid

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Role of alternative polyadenylation dynamics in acute myeloid leukaemia at single-cell resolution

RNA Biology ◽

10.1080/15476286.2019.1586139 ◽

2019 ◽

Vol 16 (6) ◽

pp. 785-797 ◽

Cited By ~ 10

Author(s):

Congting Ye ◽

Qian Zhou ◽

Yiling Hong ◽

Qingshun Quinn Li

Keyword(s):

Acute Myeloid Leukaemia ◽

Single Cell ◽

Myeloid Leukaemia ◽

Alternative Polyadenylation ◽

Acute Myeloid

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N6-Methyladenosine Role in Acute Myeloid Leukaemia

International Journal of Molecular Sciences ◽

10.3390/ijms19082345 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2345 ◽

Cited By ~ 13

Author(s):

Zaira Ianniello ◽

Alessandro Fatica

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Cellular Differentiation ◽

Normal Development ◽

Rna Modifications ◽

Deep Impact ◽

Rna Molecules ◽

Post Transcriptional Regulation ◽

Acute Myeloid

We are currently assisting in the explosion of epitranscriptomics, which studies the functional role of chemical modifications into RNA molecules. Among more than 100 RNA modifications, the N6-methyladenosine (m6A), in particular, has attracted the interest of researchers all around the world. m6A is the most abundant internal chemical modification in mRNA, and it can control any aspect of mRNA post-transcriptional regulation. m6A is installed by “writers”, removed by “erasers”, and recognized by “readers”; thus, it can be compared to the reversible and dynamic epigenetic modifications in histones and DNA. Given its fundamental role in determining the way mRNAs are expressed, it comes as no surprise that alterations to m6A modifications have a deep impact in cell differentiation, normal development and human diseases. Here, we review the proteins involved in m6A modification in mammals, m6A role in gene expression and its contribution to cancer development. In particular, we will focus on acute myeloid leukaemia (AML), which provides an initial indication of how alteration in m6A modification can disrupt normal cellular differentiation and lead to cancer.

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