Background: Neutrophil PRV-1 over-expression has been strongly associated with polycythemia vera (PV) and its quantitative measurement might complement the diagnostic distinction between PV and secondary polycythemia (

Klippel et al. Blood 2003;102:3569
). Furthermore, the PV-specificity of the particular abnormality had been suggested by studies that demonstrated increased PRV-1 expression in post-polycythemic but not agnogenic myeloid metaplasia (
Tefferi et al. Blood 2003;103:3547
) as well as by other studies that suggested the inevitable progression into PV of essential thrombocythemia (ET) associated with PRV-1 over-expression (
Griesshammer et al. Ann Hematol 2004;83:364
). Still others have suggested the possibile utility of the particular assay in differentiating clonal from reactive myeloproliferation (
Cilloni et al. Blood 2004;103:2428
).

Methods: The purpose of the current study was two-fold; i) to further evaluate the specificity of neutrophil PRV-1 over expression to either PV or clonal myeloproliferation by testing the assay in atypical myeloproliferative disorders (AMPD) and ii) to evaluate eosinophil PRV-1 expression in AMPD associated with eosinophilia. In a prospective study, 13 patients with AMPD and 2 with reactive eosinophilia were evaluated for neutrophil PRV-1 expression (table 1). PRV-1 transcript quantitation was performed according to published methods (

Klippel et al. Blood 2003;102:3569
). PRV-1 gene expression was considered elevated in the presence of a PRV-1/GAPDH ratio of 1.17 or lower.

Table 1

PatientDiagnosisNeutrophil PRV-1/GAPDH ratioNeutrophil PRV-1 expression
1 Chronic myelomonocytic leukemia associated with myelofibrosis 1.05 Increased 
2 FIP1L1/PDGFRA-positive eosinophilic disorder 1.39 Normal 
3 FIP1L1/PDGFRA-positive eosinophilic disorder 1.19 Normal 
4 FIP1L1/PDGFRA-positive eosinophilic disorder 1.10 Increased 
5 Biphenotypic acute leukemia with prominent blood eosinophilia 0.99 Increased 
6 Hypereosinophilic syndrome with cardiac involvement 1.15 Increased 
7 Hypereosinophilic syndrome with cardiac involvement 1.13 Increased 
8 Hypereosinophilic syndrome with sinus involvement 1.29 Normal 
9 Reactive eosinophilia associated with atopic dermatitis 1.09 Increased 
10 Reactive eosinophilia associated with T cell skin lymphoma 1.22 Normal 
11 Aggressive systemic mastocytosis associated with chronic myelomonocytic leukemia 1.08 Increased 
12 Aggressive systemic mastocytosis associated with myelofibrosis 1.09 Increased 
13 Aggressive systemic mastocytosis with circulating mast cells 1.29 Normal 
14 Indolent systemic mastocytosis 1.20 Normal 
15 Indolent systemic mastocytosis 1.18 Normal 
PatientDiagnosisNeutrophil PRV-1/GAPDH ratioNeutrophil PRV-1 expression
1 Chronic myelomonocytic leukemia associated with myelofibrosis 1.05 Increased 
2 FIP1L1/PDGFRA-positive eosinophilic disorder 1.39 Normal 
3 FIP1L1/PDGFRA-positive eosinophilic disorder 1.19 Normal 
4 FIP1L1/PDGFRA-positive eosinophilic disorder 1.10 Increased 
5 Biphenotypic acute leukemia with prominent blood eosinophilia 0.99 Increased 
6 Hypereosinophilic syndrome with cardiac involvement 1.15 Increased 
7 Hypereosinophilic syndrome with cardiac involvement 1.13 Increased 
8 Hypereosinophilic syndrome with sinus involvement 1.29 Normal 
9 Reactive eosinophilia associated with atopic dermatitis 1.09 Increased 
10 Reactive eosinophilia associated with T cell skin lymphoma 1.22 Normal 
11 Aggressive systemic mastocytosis associated with chronic myelomonocytic leukemia 1.08 Increased 
12 Aggressive systemic mastocytosis associated with myelofibrosis 1.09 Increased 
13 Aggressive systemic mastocytosis with circulating mast cells 1.29 Normal 
14 Indolent systemic mastocytosis 1.20 Normal 
15 Indolent systemic mastocytosis 1.18 Normal 
View Large

In addition, eosinophil PRV-1 expression was measured in 2 patients from the above cohort (patients 3 and 8) and 3 additional patients with hypereosinophilic syndrome (HES).

Results: Table 1 outlines specific diagnoses as well as the corresponding neutrophil PRV-1 expression levels in all 15 patients tested (median age 54 years, range 20–74; 11 males). Eosinophil PRV-1 expression was normal in all 5 patients tested (range of PRV-1/GAPDH ratio between 1.20–1.39).

Conclusion: The current study suggests that neutrophil PRV-1 over-expression is a non-specific marker of clonal myeloproliferation that is seen in a broad spectrum of both typical and atypical myeloid disorders. As has been the case in ET, only a subset of AMPD patients display the specific abnormality, thus undermining its diagnostic utility. The preliminary information from the current study does not suggest increased eosinophil PRV-1 expression in either HES or clonal eosinophilia.

Topics:
atypical, eosinophils, myeloproliferative disease, neutrophils, eosinophilia, disseminated eosinophilic collagen disease, primary eosinophilic endomyocardial cardiomyopathy, mastocytosis, aggressive systemic, platelet-derived growth factor alpha receptor, cardiovascular findings

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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