Baxter EJ

Ho CL

Hrabec E

Jensen MK

Kjeldsen L

Marquez-Curtis LA

Murate T

O’Connell JP

Passamonti F

Rameshwar P

Reilly JT

Thiele J

Van Lint P

Wang JC

&lt;i&gt;Background/Aims:&lt;/i&gt; Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share the same acquired lesion JAK2&lt;sup&gt;V617F&lt;/sup&gt; and may exhibit substantial overlap. Variability in JAK activation and allele burden, complemented by host, genetic and non-genetic modifiers, determine the phenotype. The aim of this study was to investigate the presence of the JAK2 mutation in association with the ratio of metallopeptidases inhibitors (TIMPs) to tissue metallopeptidases (MMPs) in MPNs, where inhibitory rather than proteolytic activity in marrow microenvironment appears to predominate. &lt;i&gt;Methods:&lt;/i&gt; 94 patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis, and 102 healthy individuals were evaluated. Allele-specific PCR and RFLP were used to detect JAK2 and genomic status. Serum concentrations of MMP and TIMP were measured by ELISA. The parameters were assessed with covariance analysis, and adjusted for gender, age and co-morbidity. &lt;i&gt;Results:&lt;/i&gt; Mutation frequency was 81.91%. Abnormal TIMP/MMP ratios were identified in all three diseases. JAK2 mutation was correlated with significant changes in TIMP concentrations. &lt;i&gt;Conclusions:&lt;/i&gt; Identification of an abnormal TIMP/MMP ratio in all three diseases, regardless of the JAK2 status, indicates invariable marrow remodeling. In this particular group of patients, presence of a JAK2&lt;sup&gt;V617F&lt;/sup&gt; mutation, being associated with even higher ratios, appears to be a concurring participant in bone marrow-reforming processes. Additional research may delineate correlates with the JAK2 allelic burden.</jats:p

C.M. Vadikolia

C. Tsatalas

K. Anagnostopoulos

G. Trypsianis

D. Pantelidou

I. Bazdiara

A. Anastasiadis

E. Spanoudakis

I. Kotsianidis

D. Margaritis

A. Kortsaris

G. Bourikas

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Acta Haematologica

Proteolytic Matrix Metallopeptidases and Inhibitors in BCR-ABL1-Negative Myeloproliferative Neoplasms: Correlation with JAK2&lt;sup&gt;V617F&lt;/sup&gt; Mutation Status

Proteolytic Matrix Metallopeptidases and Inhibitors in BCR-ABL1-Negative Myeloproliferative Neoplasms: Correlation with JAK2<sup>V617F</sup> Mutation Status

Proteolytic Matrix Metallopeptidases and Inhibitors in BCR-ABL1-Negative Myeloproliferative Neoplasms: Correlation with JAK2<sup>V617F</sup> Mutation Status

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