Extending Jak2V617F and MplW515 Mutation Analysis to Single Hematopoietic Colonies and B and T Lymphocytes
Article first published online: 31 MAY 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 9, pages 2358–2362, September 2007
How to Cite
Pardanani, A., Lasho, T. L., Finke, C., Mesa, R. A., Hogan, W. J., Ketterling, R. P., Gilliland, D. G. and Tefferi, A. (2007), Extending Jak2V617F and MplW515 Mutation Analysis to Single Hematopoietic Colonies and B and T Lymphocytes. STEM CELLS, 25: 2358–2362. doi: 10.1634/stemcells.2007-0175
- Issue published online: 2 JAN 2009
- Article first published online: 31 MAY 2007
- Manuscript Accepted: 19 MAY 2007
- Manuscript Received: 13 MAR 2007
- Hematopoietic progenitor cells;
- Human CD34 and CD43 cells;
- Colony formation;
- JAK kinase;
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.
Disclosure of potential conflicts of interest is found at the end of this article.