Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens.
OBJECTIVE
The myeloproliferative disorders (MPD), polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), differ phenotypically, but share the same JAK2(V617F) mutation. We examined the relationship of the quantitative JAK2(V617F) allele burden to MPD disease phenotype among the three MPD classes and within PV.


METHODS
We measured the JAK2(V617F) allele percentage in genomic DNA from neutrophils, CD34(+) cells, and cloned progenitors in 212 JAK2(V617F)-positive MPD patients and correlated the allele burdens to both disease class and disease features.


RESULTS
In ET and PV, mean CD34(+) cell JAK2(V617F) allele burdens were lower than the corresponding neutrophil allele burdens, but these were equivalent in PMF. JAK2(WT) progenitors were present in ET and PV when the CD34(+) JAK2(V617F) allele burden was lower than the neutrophil allele burden, but not in PV and PMF subjects in whom the CD34(+) cell and neutrophil allele burdens were similar. CD34(+) cell JAK2(V617F) clonal dominance, defined as coherence between the CD34(+) cell and neutrophil JAK2(V617F) allele burdens, was present in 24% of ET, 56% of PV, and 93% of PMF patients, and was independent of the CD34(+) cell JAK2(V617F) genotype. Clonally dominant PV patients had significantly longer disease durations, higher white cell counts, and larger spleens than nondominant PV patients.


CONCLUSIONS
We conclude that the extent of JAK2(V617F) CD34(+) cell clonal dominance is associated with disease phenotype within the MPD and, in PV, is associated with extramedullary disease, leukocytosis, and disease duration.
Moliterno
Alison R
AR
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. amoliter@jhmi.edu
Williams
Donna M
DM
Rogers
Ophelia
O
Isaacs
Mary Ann
MA
Spivak
Jerry L
JL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009504:Neutrophils / Q000502:physiology*; D010641:Phenotype; D011087:Polycythemia Vera / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics
C507924:JAK2 protein, human; D053614:Janus Kinase 2