Acquired Aplastic Anemia

A, Biopsy specimen of bone marrow (hematoxylin-eosin, low magnification). B, Magnetic resonance imaging scan of the spine shows uniform replacement of bone marrow with fat. C, Long-term bone marrow culture-initiating cell number as a surrogate of stem cell number. Horizontal bars indicate mean values.

Infection of hematopoietic stem cells by a virus (shown here) or introduction of a drug into hematopoietic stem cells and chemical modification of cell proteins may lead to the production of neoantigens (red squares). As part of this process, normal cell proteins may be overexpressed (brown half circles) or aberrantly expressed (blue triangles), that is, synthesized in cells that normally do not produce them. Antigen-presenting cells (not shown) process the neoantigens and cell surface proteins into peptides and present them via major histocompatibility complex molecules to quiescent T cells. During the normal immune response, activation of T cells that recognize the neoantigens and T cells that recognize the overexpressed and aberrantly expressed cell proteins (self-reactive T cells) leads to immune destruction of target cells by Fas/Fas ligand-mediated apoptosis (nuclear degeneration indicated by interrupted outlines around nuclei followed by cell death indicated by faded cells). In autoimmune disease, after the normal immune response is complete (for example, destruction of infected cells expressing viral proteins), predominantly self-reactive T cells perpetuate tissue destruction. Chronic T-cell attack may favor the emergence of clones of hematopoietic stem cells that are not susceptible to immune cell recognition (as in paroxysmal nocturnal hemoglobinuria [PNH]) or that resist apoptotic cell death (as in myelodysplasia [MDS]).