Quantification of IGF-1 Receptor May Be Useful in Diagnosing Polycythemia Vera–Suggestion to Be Added to Be One of the Minor Criterion

Endogenous erythroid colony (EEC) formation is one of the minor criteria for diagnosing polycythemia vera (PV) according to 2008 WHO diagnostic criteria. But EEC requires bone marrow aspiration and sophisticated laboratory procedures; therefore, practically it is rarely used to diagnose PV. Insulin-like growth factor 1 receptor (IGF-1R) was found to be constitutively phosphorylated and was responsible for the EEC formation in PV; therefore, we measured IGF-1R levels in the peripheral blood of 26 PV patients and compared them with those of 33 patients with secondary polycythemia and 29 normal controls. Among the PV patients, 16 were treated with only phlebotomy, 9 received hydroxyurea, and 1 was treated with ruxolinitinib. We found that PV patients treated with only phlebotomy had significantly higher IGF-1R levels than did those PV patients treated with hydroxyurea or ruxolinitinib. None of the secondary PV patients or normal controls had elevated IGR-1R levels, while 14 of 16 (87%) PV patients had significantly elevated IGF-1R levels. The new 2016 WHO has eliminated EEC as a minor criterion for diagnosing PV, but there are still some cases that cannot be definitively diagnosed by the current criteria. Therefore, we suggest that quantifying the IGF-1R level in peripheral blood by flow cytometry to replace EEC as the minor criterion for diagnosing PV.

[1]  T. Barbui,et al.  Masked polycythemia Vera (mPV): Results of an international study , 2018, American journal of hematology.

[2]  Mario Cazzola,et al.  The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. , 2016, Blood.

[3]  T. Barbui,et al.  Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis , 2015, Blood Cancer Journal.

[4]  F. Climent,et al.  WHO‐histological criteria for myeloproliferative neoplasms: reproducibility, diagnostic accuracy and correlation with gene mutations and clinical outcomes , 2014, British journal of haematology.

[5]  S. Ascani,et al.  Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms , 2014, Modern Pathology.

[6]  R. Silver,et al.  Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis. , 2013, Blood.

[7]  H. Choi,et al.  Allelic Expression Imbalance of JAK2 V617F Mutation in BCR-ABL Negative Myeloproliferative Neoplasms , 2013, PloS one.

[8]  J. Thiele,et al.  Prodromal myeloproliferative neoplasms: The 2008 WHO classification , 2009, American journal of hematology.

[9]  A. Zanella,et al.  The significance of bone marrow biopsy and JAK2V617F mutation in the differential diagnosis between the "early" prepolycythemic phase of polycythemia vera and essential thrombocythemia. , 2008, American Journal of Clinical Pathology.

[10]  P. Guglielmelli,et al.  Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal , 2008, Leukemia.

[11]  C. Bloomfield,et al.  Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. , 2007, Blood.

[12]  A. Tefferi,et al.  Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera , 2007, Leukemia.

[13]  S. Constantinescu,et al.  JAK1 and Tyk2 Activation by the Homologous Polycythemia Vera JAK2 V617F Mutation , 2005, Journal of Biological Chemistry.

[14]  V. Diehl,et al.  Initial (Latent) Polycythemia vera with Thrombocytosis Mimicking Essential Thrombocythemia , 2005, Acta Haematologica.

[15]  V. Diehl,et al.  Bone marrow features of diagnostic impact in erythrocytosis , 2005, Annals of Hematology.

[16]  J. Spivak,et al.  Polycythemia vera: myths, mechanisms, and management. , 2002, Blood.

[17]  Paulo N. Correa,et al.  Increased basal and induced tyrosine phosphorylation of the insulin-like growth factor I receptor beta subunit in circulating mononuclear cells of patients with polycythemia vera. , 1995, Blood.

[18]  S. Geller,et al.  Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies. , 1986, Seminars in hematology.

[19]  N. Casadevall,et al.  Polycythaemia Vera: in Vitro Studies of Circulating Erythroid Progenitors , 1980, British journal of haematology.

[20]  R. Hoffman,et al.  Erythroid colony formation by polycythemia vera bone marrow in vitro. Dependence on erythropoietin. , 1977, The Journal of clinical investigation.

[21]  Peter J Campbell,et al.  Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. , 2008, Blood.

[22]  J. Thiele,et al.  Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). , 2005, Histology and histopathology.

[23]  F. Girodon,et al.  Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis. , 2004, Haematologica.

[24]  Paulo N. Correa,et al.  Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium. , 1994, Blood.

[25]  B. Alter,et al.  Comparison of erythroid progenitor cell growth in vitro in polycythemia vera and chronic myelogenous leukemia: only polycythemia vera has endogenous colonies. , 1989, Leukemia research.

[26]  R. Levere,et al.  Endogenous erythroid colony formation by peripheral blood mononuclear cells from patients with myelofibrosis and polycythemia vera. , 1979, Acta haematologica.

[27]  C. Eaves,et al.  Erythropoietin (Ep) dose-response curves for three classes of erythroid progenitors in normal human marrow and in patients with polycythemia vera. , 1978, Blood.

[28]  A. Axelrad,et al.  Letter: Bone-marrow responses in polycythemia vera. , 1974, The New England journal of medicine.