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TRANSLATIONAL AND CLINICAL RESEARCH |
aDivisions of Hematology and
bLaboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA;
cDana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA;
dHoward Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA
Key Words. Hematopoietic progenitor cells • Human CD34 and CD43 cells • Colony formation • JAK kinase • Myelopoiesis
Correspondence: Ayalew Tefferi, M.D., Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. Telephone: 507-284-3159; Fax: 507-266-4972; e-mail: tefferi.ayalew{at}mayo.edu
Received March 13, 2007;
accepted for publication May 19, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS May 31, 2007.
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.
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