TY - JOUR
T1 - Clonal analyses define the relationships between chromosomal abnormalities and JAK2V617F in patients with Ph-negative myeloproliferative neoplasms*
AU - Wang, Xiaoli
AU - LeBlanc, Amanda
AU - Gruenstein, Steven
AU - Xu, Mingjiang
AU - Mascarenhas, John
AU - Panzera, Brenda
AU - Wisch, Nathaniel
AU - Parker, Charles
AU - Goldberg, Judith D.
AU - Prchal, Josef
AU - Hoffman, Ronald
AU - Najfeld, Vesna
N1 - Funding Information:
This study was support by grants from the Myeloproliferative Disorders Foundation (Chicago, IL, USA) (to R.H.), National Cancer Institute (Bethesda, MD, USA) (1P01CA108671 to R.H.) and the Department of Defense (Washington DC, USA).
PY - 2009/10
Y1 - 2009/10
N2 - Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=70249085509&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2009.07.003
DO - 10.1016/j.exphem.2009.07.003
M3 - Article
C2 - 19615425
AN - SCOPUS:70249085509
SN - 0301-472X
VL - 37
SP - 1194
EP - 1200
JO - Experimental Hematology
JF - Experimental Hematology
IS - 10
ER -