Acquired α Thalassemia in Association with Myelodysplastic Syndrome and Other Hematologic Malignancies

Abnormalities of hemoglobin synthesis are usually inherited, but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with a high incidence of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired α thalassemia is the most well characterized of the acquired red cell disorders described in the setting of hematologic malignancy, and is almost always associated with a myelodysplastic syndrome (MDS). At least two molecular mechanisms for acquired α thalassemia are now recognized: acquired deletion of the α globin gene cluster limited to the neoplastic clone, and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX that cause dramatic down-regulation of α globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of α thalassemia arising in the setting of a clonal myeloid disorder, and we discuss how ATRX might affect gene expression in normal and abnormal hematopoiesis via epigenetic mechanisms. only. For personal use at PENN STATE UNIVERSITY on February 23, 2013. bloodjournal.hematologylibrary.org From