Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH).

Abstract

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.

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@article{Inoue2006MolecularBO, title={Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH).}, author={Norimitsu Inoue and Tomohisa Izui-Sarumaru and Yoshiko Idate Murakami and Yuichi Endo and Jun-ichi Nishimura and Ken Kurokawa and Maki Kuwayama and Hiroaki Shime and Takashi Machii and Yuzuru Kanakura and Gabrielle Meyers and Carl T. Wittwer and Zhong Chen and William Babcock and Debra A Frei-Lahr and Charles Parker and Taroh Kinoshita}, journal={Blood}, year={2006}, volume={108 13}, pages={4232-6} }