Autoimmune lymphoproliferative syndromes are characterized by chronic accumulation of nonmalignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies. ALPS IV is the first form known to be caused by abnormal intrinsic pathway ... Autoimmune lymphoproliferative syndromes are characterized by chronic accumulation of nonmalignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies. ALPS IV is the first form known to be caused by abnormal intrinsic pathway apoptosis (summary by Oliveira et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of ALPS, see 601859.
Oliveira et al. (2007) reported a 49-year-old patient with autoimmune lymphoproliferative syndrome who had a lifelong overexpansion of lymphocytes and a history of childhood leukemia and early adulthood lymphoma, both successfully treated. There were no developmental defects. Laboratory ... Oliveira et al. (2007) reported a 49-year-old patient with autoimmune lymphoproliferative syndrome who had a lifelong overexpansion of lymphocytes and a history of childhood leukemia and early adulthood lymphoma, both successfully treated. There were no developmental defects. Laboratory studies showed increased serum alpha/beta, CD4-/CD8- T cells and lymph node follicular hyperplasia. There was no evidence of CD95 (134637)-mediated apoptosis, but the patient's lymphocytes resisted death by IL2 (147680) withdrawal, indicating a specific defect in lymphocyte apoptosis. Further studies of the patient's cells indicated a decrease of the proapoptotic protein BIM (BCL2L11; 603827), which is critical for withdrawal-induced mitochondrial apoptosis.
In a patient with ALPS type IV, Oliveira et al. (2007) identified a heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp substitution (G13D; 164790.0003). In vitro functional expression studies showed that the G13D mutation resulted ... In a patient with ALPS type IV, Oliveira et al. (2007) identified a heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp substitution (G13D; 164790.0003). In vitro functional expression studies showed that the G13D mutation resulted in increased activation of NRAS.