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. 2008 Nov;36(11):1480-6.
doi: 10.1016/j.exphem.2008.05.006. Epub 2008 Aug 23.

Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens

Alison R Moliterno  1 , Donna M Williams, Ophelia Rogers, Mary Ann Isaacs, Jerry L Spivak
Affiliations

Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens

Alison R Moliterno et al. Exp Hematol. 2008 Nov.

Abstract

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.

Materials and 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.

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Figures

Figure 1
Figure 1
Quantitative JAK2V617F allele burden in neutrophils and CD34+ cells obtained from the same blood sample in 17 ET, 64 PV and 15 PMF patients. Medians are indicated by bars, coincident points are overlapping.
Figure 2
Figure 2
Relationship of BFUe JAK2V617F genotypes to MPD subtype, disease duration, sex, splenomegaly, and measured CD34+ cell and neutrophil JAK2V617F allele burdens in 25 patients. On average, 27 colonies were plucked from each cloning experiment (range 20–40). Clear bars indicate a JAK2WT genotype, striped a heterozygous JAK2V617F genotype and black a homozygous JAK2V617F genotype. Asterisks above case number (top) indicate antecedent history of ET in all cases with the exception of 25, where there was an antecedent history of PV.
Figure 3
Figure 3
Relationship of Neutrophil JAK2V617F allele burden to CD34 cell JAK2V617F allele burden in 17 ET, 64 PV and 15 PMF patients. Dotted line indicates the regression line for an R=1.0 for reference.
See this image and copyright information in PMC

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