Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism.
Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1) is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype.
Chiabrando
Deborah
D
Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Tolosano
Emanuela
E
Blood. 2007 Apr 15;109(8):3152-4
17164339
PLoS One. 2009;4(1):e4152
19129914
Biochim Biophys Acta. 2009 Oct;1792(10):1036-42
19689926
Blood. 2002 Oct 15;100(8):2724-31
12351378
Blood Cells Mol Dis. 2005 Sep-Oct;35(2):189-92
15996880
Cell. 2004 Sep 17;118(6):757-66
15369674
Blood. 2003 Jun 15;101(12):5039-45
12586610
PLoS One. 2006 Dec 20;1:e37
17183665
Eur J Cell Biol. 1990 Feb;51(1):140-50
2328735
Microbiol Mol Biol Rev. 1998 Mar;62(1):1-34
9529885
Mol Ther. 2005 Apr;11(4):627-37
15771965
Br J Haematol. 2008 Sep;142(6):859-76
18671700
J Biol Chem. 2006 May 12;281(19):13309-13316
16531401
Blood. 2008 Dec 15;112(13):5228-37
18515656
Blood. 2005 Jun 15;105(12):4627-34
15626736
Mol Ther. 2003 May;7(5 Pt 1):613-22
12718904
Hum Mol Genet. 2008 Oct 15;17(20):3204-11
18653748
Blood Cells Mol Dis. 2006 Mar-Apr;36(2):259-64
16458028
Metabolism. 1989 Jan;38(1):52-6
2909829
Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):107-18
16487043
Br J Haematol. 2010 Feb;148(4):611-22
19958353
Mol Cell Biol. 2001 Jul;21(13):4246-55
11390653
Haematologica. 2008 Nov;93(11):1617-26
18815190
Exp Hematol. 2008 Nov;36(11):1428-35
18715690
Mol Cell Proteomics. 2007 Mar;6(3):382-93
17151020
FEBS Lett. 2007 Jun 19;581(15):2783-93
17509569
Blood Cells Mol Dis. 2007 Jul-Aug;39(1):35-43
17376718
Stem Cells. 2008 Feb;26(2):323-9
17962699
Horm Metab Res. 1989 Jan;21(1):11-4
2925149
Hum Mol Genet. 2008 May 1;17(9):1253-63
18230666
EMBO J. 2003 Nov 17;22(22):6068-77
14609953
Antioxid Redox Signal. 2010 Feb;12(2):305-20
19650691
Mol Cell Biol. 2004 May;24(9):4032-7
15082795
Metabolism. 1989 Aug;38(8):759-62
2474743
Nat Med. 2008 Feb;14(2):125-33
18246078
Br J Haematol. 2008 Feb;140(3):348-59
18217898
Blood. 2000 Feb 1;95(3):1093-9
10648427
Blood. 2003 Jan 1;101(1):318-24
12393682
Science. 2008 Feb 8;319(5864):825-8
18258918
J Virol. 1999 Aug;73(8):6500-5
10400745
Blood. 2005 Jun 15;105(12):4620-6
15755903
FEBS Lett. 2009 Jun 18;583(12):2049-53
19454283
Semin Hematol. 2006 Jul;43(3):167-77
16822459
Hum Mutat. 2008 Nov;29(11):E263-70
18781615
Cell Cycle. 2007 Jan 1;6(1):20-4
17245121
Trends Biochem Sci. 1995 Mar;20(3):105-8
7709427
Hum Mutat. 2008 Jul;29(7):911-20
18412286