Cyclic hematopoiesis (CH) is a rare hematological disease caused byoscillatory production of blood cells by the marrow. CH occurs sporadicay usually in children, and in families autosomal dominant disorder. At 21 day intervals, patients regularly have severe neutropenia, fever, oropharyngeal inflammation and, on occasion, severe life-threatening infections. An analogous autosomal recessive disease occurs in grey collie dogs whose blood cells oscillate with 14 day periodicity. The applicants have identified and began evaluating five families with autosomal dominant cyclic hematopoiesis (ADCH) in order to utilize reverse genetics to identify the genetic locus. Preliminary statistical analyses of the families indicates that it is highly likely that this can be accomplished through linkage analysis. Using similar methods the applicants will investigate the genetic mechanisms of the disease in the collies. In the collies, the applicants have recently learned that recombinant canine G-CSF fully corrects the hematologic abnormality and propose further studies including the use of other canine growth factors, to investigate hematopoietic regulation in this interesting disorder.
Showing the most recent 10 out of 24 publications
