Abnormal telomere shortening in leucocytes of children with Shwachman–Diamond syndrome

• Published in: British journal of haematology Vol. 117; no. 1; pp. 189 - 192
• Main Authors: Thornley, Ian, Dror, Yigal, Sung, Lilian, Wynn, Rob F., Freedman, Melvin H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.04.2002; Blackwell; Blackwell Publishing Ltd
• Subjects: Adolescent; Biological and medical sciences; Case-Control Studies; Cell Division; Child; Child, Preschool; Female; haemopoietic stem cell; Hematologic and hematopoietic diseases; Hematologic Diseases - etiology; Hematologic Diseases - pathology; Hematology; Hematopoietic Stem Cells - ultrastructure; Humans; Infant; inherited bone marrow failure; Least-Squares Analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes - ultrastructure; Male; Medical sciences; myelodysplastic syndrome; Shwachman–Diamond syndrome; Telomere - ultrastructure; telomeres; Human; Cell proliferation; Stem cell; Diseases of the osteoarticular system; Hematopoietic cell; Malignant hemopathy; Telomere; Cytopenia; Myelodysplastic syndrome; Genetic disease; Shwachman Diamond syndrome; Bone marrow failure; Digestive diseases
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03371.x

Haemopoietic dysfunction, ranging from single‐lineage cytopenia to severe aplasia and/or myelodysplasia (MDS), is prominent in Shwachman–Diamond syndrome (SDS). To assess haemopoietic stem cell proliferation in SDS, we compared leucocyte telomere length in 12 patients with SDS to that of 41 controls, using an in‐gel hybridization technique. SDS patients had an age‐adjusted mean telomere length 1·4 kilobase pairs (kbp) shorter than controls (P < 0·0001). Patients with'non‐severe′ SDS (one‐ or two‐lineage cytopenias; no MDS) had shortened telomeres (−1·4 kbp; P = 0·0004), as did those with ‘severe’ SDS. We conclude that stem cell hyperproliferation is a feature of SDS from its outset.