JAK2(V617F) mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones

Leuk Res. 2010 Jun;34(6):821-3. doi: 10.1016/j.leukres.2009.09.016. Epub 2009 Oct 9.

Abstract

The 2008 World Health Organization (WHO) proposed revision of the classification of MDS recognizes a deletion (5q) subtype with mutation of Janus kinase-2 (JAK2(V617F)). We investigated the clonal origin of this gene mutation in a patient with del(5q) MDS presenting with thrombocytosis and normal hemoglobin. Analysis of colony forming units-granulocyte-monocyte (CFU-GM) and erythropoietin-independent growth of bone marrow (BM) and peripheral blood (PB) burst forming units-erythroid (BFU-E) showed that del(5q) and JAK2(V617F) existed in progenitors derived from independent clones. Fifty percent of endogenous erythroid colonies (EEC) harbored the JAK2(V617F) mutation whereas fluorescent in situ hybridization (Fish) with a chromosome 5 (q31.1) probe showed only a diploid allele compliment. Assessment of transcriptional clonality by iduronate-2-sulfatase (IDS) gene polymorphism suggested that JAK2(V617F) was acquired in at least two independent multipotent stem cell progeny. Our findings indicate that JAK2(V617F) mutant clones may arise in genetically discordant clones independent of del(5q).

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 5*
  • Clone Cells / metabolism
  • Clone Cells / pathology*
  • Erythroid Precursor Cells / metabolism
  • Erythroid Precursor Cells / pathology
  • Female
  • Humans
  • Janus Kinase 2 / genetics*
  • Middle Aged
  • Mutation, Missense / physiology
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Phenylalanine / genetics
  • Valine / genetics

Substances

  • Phenylalanine
  • JAK2 protein, human
  • Janus Kinase 2
  • Valine