Deletion of the -globin gene cluster as a cause of acquired -thalassemia in myelodysplastic syndrome
From the Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Departments of Clinical and Laboratory Haematology, City Hospitals Sunderland NHS Trust, Tyne and Wear, United Kingdom.'j, http://www.100md.com
Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of {alpha} -thalassemia ({alpha} -thalassemia in myelodysplastic syndrome [ATMDS]) characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling gene, have recently been found in 12 patients with typical features of ATMDS, though they have not been detected in MDS patients with similar red blood cell findings but little HbH. The {alpha} -globin genes themselves have appeared normal in all ATMDS patients studied to date. Here we characterize the molecular defect in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost a greater than 1.9-Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both {alpha} -globin genes. Red blood cell changes associated with this acquired somatic genotype (––/{alpha} {alpha} ) 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.'j, http://www.100md.com
Related Articles in Blood Online :'j, http://www.100md.com
The myelodysplastic syndromes: heterogeneneity on many levels.'j, http://www.100md.com
Peter T. Curtin Blood 2004 103: 1181-1182. [Full Text](David P. Steensma Vip Viprakasit Alex Hendrick David K. Goff Joanne Leach Richard J. Gibbons and Dou)
Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of {alpha} -thalassemia ({alpha} -thalassemia in myelodysplastic syndrome [ATMDS]) characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling gene, have recently been found in 12 patients with typical features of ATMDS, though they have not been detected in MDS patients with similar red blood cell findings but little HbH. The {alpha} -globin genes themselves have appeared normal in all ATMDS patients studied to date. Here we characterize the molecular defect in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost a greater than 1.9-Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both {alpha} -globin genes. Red blood cell changes associated with this acquired somatic genotype (––/{alpha} {alpha} ) 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.'j, http://www.100md.com
Related Articles in Blood Online :'j, http://www.100md.com
The myelodysplastic syndromes: heterogeneneity on many levels.'j, http://www.100md.com
Peter T. Curtin Blood 2004 103: 1181-1182. [Full Text](David P. Steensma Vip Viprakasit Alex Hendrick David K. Goff Joanne Leach Richard J. Gibbons and Dou)