Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH)
| Autor: | Gabrielle Meyers, William Babcock, Yoshiko Murakami, Charles J. Parker, Ken Kurokawa, Junichi Nishimura, Yuzuru Kanakura, Taroh Kinoshita, Hiroaki Shime, Norimitsu Inoue, Debra Frei-Lahr, Takashi Machii, Yuichi Endo, Carl T. Wittwer, Tomohisa Izui-Sarumaru, Zhong Chen, Maki Kuwayama |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Immunology Red Cells Clone (cell biology) Hemoglobinuria Paroxysmal Biology Biochemistry Hemolysis Germline mutation hemic and lymphatic diseases Neoplasms medicine Biomarkers Tumor Humans Chromosomes Human Pair 12 Membrane Proteins Cell Biology Hematology medicine.disease Hematopoiesis Gene Expression Regulation Neoplastic Haematopoiesis medicine.anatomical_structure Mutation Paroxysmal nocturnal hemoglobinuria Ectopic expression Hemoglobinuria Female Bone marrow Stem cell |
| Popis: | Somatic mutation of PIGA in hematopoietic stem cells causes deficiency of glycosyl phosphatidylinositol–anchored proteins in paroxysmal nocturnal hemoglobinuria (PNH) that underlies the intravascular hemolysis but does not account for expansion of the PNH clone. Immune mechanisms may mediate clonal selection but appear insufficient to account for the clonal dominance necessary for PNH to become clinically apparent. Herein, we report 2 patients with PNH whose PIGA-mutant cells had a concurrent, acquired rearrangement of chromosome 12. In both cases, der(12) had a break within the 3′ untranslated region of HMGA2, the architectural transcription factor gene deregulated in many benign mesenchymal tumors, that caused ectopic expression of HMGA2 in the bone marrow. These observations suggest that aberrant HMGA2 expression, in concert with mutant PIGA, accounts for clonal hematopoiesis in these 2 patients and suggest the concept of PNH as a benign tumor of the bone marrow. |
| Databáze: | OpenAIRE |
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