Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes

Animesh Pardanani, Terra L. Lasho, Christy Finke, Ruben A. Mesa, William J. Hogan, Rhett P. Ketterling, Dwight Gary Gilliland, Ayalew Tefferi

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

JAK2V617F and MPLW515L/K are myeloproliferative disorder (MPD)-associated mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+ cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L/K) to determine (a) the proportion of colonies harboring a particular mutation in the presence or absence of cytokines, (b) the lineage distribution of endogenous colonies for each mutation, and (c) the differences (if any) in the pattern of mutation among the various MPDs, as established by genotyping of individual colonies. Genotyping analysis revealed cohabitation of mutation-negative and mutation-positive endogenous colonies in polycythemia vera as well as other MPDs. Culture of progenitor cells harboring MPLW515L/K yielded virtually no endogenous erythroid colonies in contrast to JAK2V617F-harboring progenitor cells. The mutation pattern (i.e., relative distribution of homozygous, heterozygous, or wild-type colonies) was not a distinguishing feature among the MPDs, and MPLW515 mutations were detected in B and/or T lymphocytes in all three patients tested. These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell.

Original languageEnglish (US)
Pages (from-to)2358-2362
Number of pages5
JournalStem Cells
Volume25
Issue number9
DOIs
StatePublished - Sep 1 2007

    Fingerprint

Keywords

  • Colony formation
  • Hematopoietic progenitor cells
  • Human CD34 and CD43 cells
  • JAK kinase
  • Myelopoiesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this