Cyclic neutropenia in animals

Abstract

To the editor: Pacheco et al. [1] recently published in these pages an allometric scaling analysis of cyclic neutropenia (CN) in mammals, using as reference points the hereditary disorders in humans and in gray collie dogs [2]. They make a central assumption ‘‘that the biological defect in CN is the same in dogs and in humans.’’ However, virtually all human cases derive from mutations in the neutrophil elastase (ELA2) gene [3], whereas the disorder in dogs represents a similar hematological phenotype, in association with partial albinism, because of the defects in the adaptor protein complex 3 (AP3) b-subunit, directing trans-Golgi export of transmembrane cargo proteins to lysosomes [4]. Thus, the canine disorder better models Hermansky–Pudlak syndrome Type 2, [5] than human CN. Although the genetic defects in man and dog may share common downstream mechanisms involving elastase trafficking or elicitation of the unfolded protein response, the resultant kinetics of apoptosis induction and recovery in myeloid precursors may not be the same, and thus the assumption may not be correct.