Disease relevance of DDX10

• Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase gene, DDX10, by inversion 11 (p15q22) chromosome translocation in a patient with etoposide-related myelodysplastic syndrome [1].
• A human gene encoding a putative RNA helicase, designated DDX10, was identified 400 kb telomeric to the ataxia-telangiectasia gene at chromosome 11q22-q23 [2].
• Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia [3].
• Leukemic cells from the patient were found to express the fusion transcript of NUP98 and DDX10, which is in accordance with previously reported cases of de novo or therapy-related acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(p15q22) [4].
• Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia [4].

High impact information on DDX10

• The predicted NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly [5].
• Positional cloning showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which encodes a putative RNA helicase [5].
• DDX10 is predicted to be involved in ribosome assembly [5].
• In DDX10 and NUP98, the inv(11) breakpoints occurred within two introns of each gene and the two genes merged in-frame to produce the chimeric transcripts characteristic of this translocation [5].
• Rearrangements of DDX10 were detected in t-AML/MDS cells with inv(11), and rearrangements of HOXA9 were detected in t-AML cells with t(7;11) [6].

Biological context of DDX10

• Abnormality of the MLL gene located on chromosome 11q23 has been well known in therapy-related myeloid malignancies, but it has been reported only recently that the inv(11)(p15q22) in de novo or therapy-related myeloid malignancies results in the fusion of NUP98 on chromosome 11p15 and DDX10 on chromosome 11q22 [7].
• Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML [8].
• A processed pseudogene of DDX10 was detected at chromosome 9q21-q22 [2].
• We observed a rare trinucleotide repeat length polymorphism within the coding sequence of DDX10 [2].

Anatomical context of DDX10

• DDX10 is suggested to be involved in ribosome assembly [1].

Associations of DDX10 with chemical compounds

• The DDX10 gene encodes a putative adenosine triphosphate-dependent DEAD box RNA helicase [7].
• These observations raise a possibility that the NUP98/DDX10 fusion might be involved in imatinib resistance as well as in acute transformation of CML [4].

Analytical, diagnostic and therapeutic context of DDX10

• Reverse transcriptase-polymerase chain reaction amplification of patient RNA showed a fusion transcript of nucleoporin gene NUP98, and putative DEAD-box RNA helicase gene DDX10 [1].

References