Chromosomal Aberrations and HMGA2 Expression in Paroxysmal Nocturnal Hemoglobinuria

Sellmann L,Dührsen U,Gesk S,Scholtysik R,Klein-Hitpass L,Röth A,Nückel H

doi:10.15744/2455-7641.2.101

Abstract

Somatic, inactivating PIGA mutations in haematopoietic stem cells, followed by an unknown autoimmune selection process in favor of the mutated clone, are thought to be important events in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH).

Highlights

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with typical clinical manifestations, including intravascular hemolysis, venous thrombosis, and defective hematopoiesis [1]
There is no accepted percentage of cell purity required to detect an abnormality by Single nucleotide polymorphism (SNP) chip analysis because the detection threshold depends on the size and magnitude of the aberrations
In addition to the known PIGA mutation that has been found in hematopoietic stem cells, followed by a speculative mechanism of immunological selection in favor of the paroxysmal nocturnal hemoglobinuria (PNH) clone [6], a second clonal event was recently postulated in the pathogenesis of PNH

Summary

Introduction

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with typical clinical manifestations, including intravascular hemolysis, venous thrombosis, and defective hematopoiesis [1]. Preexisting bone marrow failure to various degrees seems to be required for the development of PNH [5,6]. PNH clones are present in a majority of patients with aplastic anemia, which is consistent with the strong immune component in the pathogenesis of this disease [7,8,9]. The presence of a low number of PNH cells, even in healthy individuals, confirms the hypothesis that defective stem cells predate the stem cell failure and depletion [11]. Unlike dysplastic clones in myelodysplastic syndrome (MDS), which harbour intrinsic defects that predispose the cells to clonal evolution, external factors, such as pressure exerted by the immune system, have for a long time been speculated to be the main causes for clonal escape in PNH [5]

Objectives

Methods

Results

Conclusion