{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:11:38Z","timestamp":1783627898078,"version":"3.55.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation\/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and <jats:italic>PRV1<\/jats:italic> gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34<jats:sup>+<\/jats:sup> hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, <jats:italic>PRV1<\/jats:italic> overexpression, and clinical and laboratory parameters.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>By real time PCR assay, we observed that <jats:italic>A1, MCL1, BIK and BID<\/jats:italic>, as well as <jats:italic>A1, BCLW<\/jats:italic> and <jats:italic>BAK<\/jats:italic> gene expression were increased in ET and PMF CD34<jats:sup>+<\/jats:sup> cells respectively, while pro-apoptotic <jats:italic>BAX<\/jats:italic> and anti-apoptotic <jats:italic>BCL2<\/jats:italic> mRNA levels were found to be lower in ET and PMF CD34<jats:sup>+<\/jats:sup> cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes <jats:italic>A1, BCL2, BCL-X<\/jats:italic>\n              <jats:sub>\n                <jats:italic>L<\/jats:italic>\n              <\/jats:sub> and <jats:italic>BCLW<\/jats:italic>. In contrast, pro-apoptotic <jats:italic>BID<\/jats:italic> and <jats:italic>BIM<\/jats:italic>\n              <jats:sub>\n                <jats:italic>EL<\/jats:italic>\n              <\/jats:sub> expression were downregulated in ET leukocytes. Increased BCL-X<jats:sub>L<\/jats:sub> protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and <jats:italic>BAX, BIK and BAD<\/jats:italic> gene expression and between <jats:italic>A1, BAX<\/jats:italic> and <jats:italic>BIK<\/jats:italic> and <jats:italic>PRV1<\/jats:italic> gene expression. A negative correlation between <jats:italic>PRV1<\/jats:italic> gene expression and platelet count was observed, as well as a positive correlation between <jats:italic>PRV1<\/jats:italic> gene expression and splenomegaly.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, <jats:italic>PRV1<\/jats:italic> and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-8722-5-2","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T19:14:57Z","timestamp":1328210097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis"],"prefix":"10.1186","volume":"5","author":[{"given":"Raquel","family":"Tognon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elainy PL","family":"Gasparotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata P","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia S","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline F","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia VB","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Kashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimas T","family":"Covas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth X","family":"Souto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Aparecida","family":"Zanichelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda P","family":"Sim\u00f5es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edola A","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,2,2]]},"reference":[{"key":"191_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/sj.leu.2404955","volume":"22","author":"A Tefferi","year":"2008","unstructured":"Tefferi A, Vardiman JW: Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. 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