A pedigree with autosomal dominant thrombocytopenia, red cell macrocytosis, and an occurrence of t(12 : 21) positive pre-B acute lymphoblastic leukemia
Details
Publication Year 2007-07, Volume 39, Issue #1, Page 107-114
Journal Title
BLOOD CELLS MOLECULES AND DISEASES
Publication Type
Journal Article
Abstract
Sampling and analyzing new families with inherited blood disorders are major steps contributing to the identification of gene(s) responsible for normal and pathologic hematopoiesis. Familial occurrences of hematological disorders alone, or as part of a syndromic disease, have been reported, and for some the underlying genetic mutation has been identified. Here we describe a new autosomal dominant inherited phenotype of thrombocytopenia and red cell macrocytosis in a four-generation pedigree. Interestingly, in the youngest generation, a 2-year-old boy presenting with these familial features has developed acute lymphoblastic leukemia characterized by a t(12;21) translocation. Tri-lineage involvement of platelets, red cells and white cells may suggest a genetic defect in an early multiliear progenitor or a stem cell. Functional assays in EBV-transformed cell lines revealed a defect in cell proliferation and tubulin dynamics. Two candidate genes, RUNX1 and FOG1, were sequenced but no pathogenic mutation was found. Identification of the underlying genetic defect(s) in this family may help in understanding the complex process of hematopoiesis. (c) 2007 Elsevier Inc. All rights reserved.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
TRANSCRIPTION FACTOR GATA-1; FAMILIAL MYELODYSPLASTIC SYNDROMES; ACUTE MYELOGENOUS LEUKEMIA; MYELOID-LEUKEMIA; MUTATIONS; MECHANISMS; RUNX1/AML1; DISORDERS; COFACTOR; PROTEIN
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Creation Date: 2007-07-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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