Deletion of the α Globin Gene Cluster as a Cause of Acquired α Thalassemia in Myelodysplastic Syndrome (ATMDS)

Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of α thalassemia (ATMDS) characterized by hypochromic, microcytic, anisopoikilocytic red cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodelling gene, have recently been found in 12 patients with typical features of ATMDS, but have not been detected in MDS cases with similar red cell findings but little HbH. The α globin genes themselves have appeared normal in all ATMDS cases studied to date. Here we characterize the molecular defect in a unique MDS case with rare HbH inclusions where an abnormal clone lost a >1.9 Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both α globin genes. The red cell changes associated with this acquired somatic genotype (--/αα) are surprisingly severe, demonstrating that a minor globin chain imbalance may be unexpectedly deleterious during the abnormal erythropoiesis that occurs in the context of MDS. For personal use only. on September 14, 2017. by guest www.bloodjournal.org From