Abstract
JAK2V617F occurs in ∼93% of patients with polycythemia vera and ∼50% of patients with either primary myelofibrosis or essential thrombocythemia. Chromosomal abnormalities are detected in 50% of patients with primary myelofibrosis, 29% with polycythemia vera, and 8% to 10% with essential thrombocythemia. The relationship between the presence of such chromosomal abnormalities and the
JAK2V617 allele burden, and the role that each of these genetic events play in the origins and progression of the myeloproliferative neoplasms (MPNs), remain unclear.
Individual hematopoietic colonies were assayed in vitro from the CD34
+ cells of six
JAK2V617F-positive MPN patients with marker chromosomal abnormalities. Colonies were simultaneously analyzed for
JAK2 genotype and chromosomal abnormalities.
Among the 248 colonies assayed from cultures containing 500 CD34
+ cells, chromosomal abnormalities were detected in 5% of colonies with wild-type
JAK2, 32% of
JAK2V617F heterozygous colonies and 56% of
JAK2V617F homozygous colonies. Overall, 92% of chromosomally abnormal colonies were also
JAK2V617F homozygous. Although 54 colonies contained wild-type
JAK2 exclusively, 4 of these colonies were characterized by chromosomal abnormalities.
This study indicates that MPN hematopoietic progenitor cells do not necessarily always acquire genetic events in the same sequence. (Chromosomally abnormal progenitor cells are closely associated with
JAK2V617F homozygosity;
p
=
0.0001.). Chromosomal abnormalities such as +8, +9 can occasionally precede acquisition of
JAK2V617F. These findings support the existence of earlier genetic events that precede
JAK2V617F or cytogenetic abnormalities in MPN hematopoietic progenitor cells.
