Lessons from familial myeloproliferative disorders

Semin Hematol. 2005 Oct;42(4):266-73. doi: 10.1053/j.seminhematol.2005.08.002.

Abstract

By definition, myeloproliferative disorders (MPDs) are caused by an acquired somatic mutation of a hematopoietic progenitor/stem cell and have sporadic occurrence. However, well-documented families exist with first-degree relatives acquiring one or several MPDs. It is reasonable to assume that the germ-line mutation(s) or genetic background must facilitate or predispose for one or several somatic mutation(s) that lead to the MPD that is indistinguishable from the sporadic form. This is best documented in familial polycythemia vera (PV), which appears to be inherited as an autosomal dominant disorder with incomplete penetrance. However, there are also families wherein members develop any combination of MPDs, including PV, essential thrombocythemia (ET), chronic myelocytic leukemia (CML), and idiopathic myelofibrosis (IMF). A separate group of familial diseases is the familial thrombocythemias, wherein germ-line mutations in the genes for thrombopoietin or its receptor, MPL, cause polyclonal hereditary thrombocythemia, which may be clinically indistinguishable from ET. Patients with the congenital polycythemic condition "primary familial and congenital polycythemia" (PFCP) have characteristically decreased erythropoietin (Epo) levels similar to PV, hypersensitive erythroid progenitors, and low Epo levels; as such, this condition is often confused with PV. Therefore, PFCP will also be discussed here, while other congenital polycythemic states such as the Chuvash polycythemia that have elevated or inappropriately normal Epo levels will be omitted from this review in view of their distinct phenotype and unique laboratory features.

Publication types

  • Review

MeSH terms

  • Chromosomes, Human, X / genetics*
  • Erythroid Precursor Cells / metabolism
  • Erythroid Precursor Cells / pathology
  • Erythropoietin / blood
  • Genetic Markers / genetics
  • Humans
  • Loss of Heterozygosity / genetics*
  • Phenotype
  • Polycythemia Vera / genetics*
  • Polycythemia Vera / metabolism
  • Polycythemia Vera / pathology

Substances

  • Genetic Markers
  • Erythropoietin