Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria.
Patients with paroxysmal nocturnal haemoglobinuria (PNH) have expanded clonal cells bearing a somatic mutation in the PIGA gene. Our previous study on two PNH patients with chromosome 12 rearrangements demonstrated the involvement of HMGA2 expression in clonal expansion. The present study investigated HMGA2 expression in PNH patients without chromosomal abnormalities. The expression of short HMGA2 with latent exon was significantly high in peripheral blood cells from 18 of 24 patients. Over-expression of truncated HMGA2 in mouse bone marrow cells caused expansion in recipient mice. These results support the idea that deregulated expression of HMGA2 causes expansion of PNH cells.
Department of Immunoregulation, Research Institute for Microbial Diseases Department of Immunoglycobiology, WPI Immunology Frontier Research Centre, Osaka, Japan.
Yoshiko
Y
Murakami
Norimitsu
N
Inoue
Tsutomu
T
Shichishima
Rieko
R
Ohta
Hideyoshi
H
Noji
Yusuke
Y
Maeda
Jun-Ichi
J
Nishimura
Yuzuru
Y
Kanakura
Taroh
T
Kinoshita
D017398:Alternative Splicing; D000741:Anemia, Aplastic / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured / Q000637:transplantation; D002999:Clone Cells / Q000473:pathology; D003114:Colony-Forming Units Assay; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014161:Transduction, Genetic
D025743:HMGA2 Protein; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C080086:phosphatidylinositol glycan-class A protein