Camaschella Clara
Vita-Salute University and San Raffaele Scientific Institute, Milan, Italy.
Semin Hematol. 2009 Oct;46(4):371-7. doi: 10.1053/j.seminhematol.2009.07.001.
Inherited sideroblastic anemia comprises several rare anemias due to heterogeneous genetic lesions, all characterized by the presence of ringed sideroblasts in the bone marrow. This morphological aspect reflects abnormal mitochondrial iron utilization by the erythroid precursors. The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation. The identification of other genes, such as adenosine triphosphate (ATP) binding cassette B7 (ABCB7) and glutaredoxin 5 (GLRX5), has strengthened the role of iron sulfur cluster biogenesis in sideroblast formation and revealed a complex interplay between pathways of mitochondrial iron utilization and cytosolic iron sensing by the iron-regulatory proteins (IRPs). As recently occurred with the discovery of the SLC25A38-related sideroblastic anemia, the identification of the genes responsible for as yet uncharacterized forms will provide further insights into mitochondrial iron metabolism of erythroid cells and the pathophysiology of sideroblastic anemia.
遗传性铁粒幼细胞贫血包括几种由异质性遗传病变引起的罕见贫血，其共同特征是骨髓中出现环形铁粒幼细胞。这一形态学特征反映了红系前体细胞线粒体铁利用异常。最常见的X连锁铁粒幼细胞贫血（XLSA）是由于血红素合成途径的首个酶——δ-氨基乙酰丙酸合酶2（ALAS2）发生突变，导致血红素缺乏与线粒体铁蓄积相关。其他基因如三磷酸腺苷（ATP）结合盒B7（ABCB7）和谷氧还蛋白5（GLRX5）的鉴定，强化了铁硫簇生物合成在铁粒幼细胞形成中的作用，并揭示了线粒体铁利用途径与铁调节蛋白（IRP）对胞质铁感知之间的复杂相互作用。正如最近发现的与SLC25A38相关的铁粒幼细胞贫血一样，鉴定出导致尚未明确特征的类型的基因，将为红系细胞的线粒体铁代谢以及铁粒幼细胞贫血的病理生理学提供进一步的见解。
