High-dose cyclophosphamide does not eradicate paroxysmal nocturnal haemoglobinuria haematopoiesis in mice carrying a Piga gene mutation.
Recently, high-dose cyclophosphamide (HD CY) has been used in the treatment of aplastic anaemia. Several reports have suggested that the treatment may either eradicate or suppress mutant clonal haematopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH). We therefore treated mice that have a proportion of blood cells deficient in GPI-anchor molecules (PIGA-) with HD CY, and monitored their peripheral blood counts during and after treatment. HD CY produced a transient myelosuppression; however, the contribution of PIGA- haematopoiesis to the peripheral blood remained unchanged, suggesting that HD CY is unlikely to eliminate an existing PNH clone in patients treated for aplastic anaemia.
Schaefer
Anne
A
Division of Hematology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Jasinski
Marek
M
Bessler
Monica
M
D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000187:drug effects; D018797:Cell Cycle Proteins; D003520:Cyclophosphamide / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics*; D006454:Hemoglobins / Q000187:drug effects; D006457:Hemoglobinuria, Paroxysmal; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007267:Injections; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D012156:Reticulocytes / Q000187:drug effects
C486565:Caprin1 protein, mouse; D018797:Cell Cycle Proteins; D006454:Hemoglobins; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D003520:Cyclophosphamide