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A 15q24 microdeletion in transient myeloproliferative disease (TMD) and acute megakaryoblastic leukaemia (AMKL) implicates PML and SUMO3 in the leukaemogenesis of TMD/AMKL.

Transient myeloproliferative disorder (TMD) of the newborn and acute megakaryoblastic leukaemia (AMKL) in children with Down syndrome (DS) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the X-chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. Here, we report the occurrence of TMD, which spontaneously remitted and later progressed to AMKL in a patient without DS but with a distinct dysmorphic syndrome. Genetic analysis of the leukaemic clone revealed somatic trisomy 21 and a truncating GATA1 mutation. The analysis of the patient's normal blood cell DNA on a genomic single nucleotide polymorphism (SNP) array revealed a de novo germ line 2·58 Mb 15q24 microdeletion including 41 known genes encompassing the tumour suppressor PML. Genomic context analysis of proteins encoded by genes that are included in the microdeletion, chromosome 21-encoded proteins and GATA1 suggests that the microdeletion may trigger leukaemogenesis by disturbing the balance of a hypothetical regulatory network of normal megakaryopoiesis involving PML, SUMO3 and GATA1. The 15q24 microdeletion may thus represent the first genetic hit to initiate leukaemogenesis and implicates PML and SUMO3 as novel components of the leukaemogenic network in TMD/AMKL.

Br. J. Haematol.2012 Apr,157(2).

Protein Name:SUMO3
Gene Name:SUMO3 SMT3B SMT3H1

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CE04

Recombinant Human SUMO3
(CatNo. CE04)

Recombinant Human Small Ubiquitin-Related Modifier 3/SUMO3 produced by our E. coli expression system. The target protein is expressed with sequence (Met1-Phe103) of Human SUMO3 fused with a 6His tag at the N-terminus.

SUMO3 belongs to the SUMO protein family and operates like ubiquitin. Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polyer. Nevertheless unlike ubiquitin that targets proteins for degration, SUMO3 takes part in several cellular processess, such as nuclear transport, transcription regulation, apoptosis and protein stability. SUMO3 participates in amyloid beta generation and has a key role in the oneset or progression of Alzheimer's disease.