Genes Located within the del(9q) Commonly Deleted Region Are Down-Regualted in Acute Myeloid Leukaemia.

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).