Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphometrical parameters of megakaryocytes was also remarked. Reticulin fibrosis was mild in 13 cases and moderate in 6 cases before IFN therapy. Reticulin content was unmodified during therapy in all cases but two, in which fibrosis changed from mild to moderate. In conclusion IFN therapy is to be considered a good method in polycythemia vera for the control of proliferative activity of bone marrow but with IFN therapy one cannot determine regression of marrow fibrosis.
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PMID:Morphometric study of the bone marrow in polycythemia vera following interferon-alpha therapy. 851 17

The role of histopathology in the diagnosis of essential thrombocythemia (ET) is controversial, and there has been little attempt to quantitate interobserver variability. Diagnostic bone marrow trephine biopsy specimens from 370 patients with ET by Polycythemia Vera Study Group (PVSG) criteria were assessed by 3 experienced hematopathologists for 16 different morphologic features and overall diagnosis according to the World Health Organization (WHO) classification. Our results show substantial interobserver variability, particularly for overall diagnosis and individual cellular characteristics such as megakaryocyte morphology. Reticulin grade was the dominant independent predictor of WHO diagnostic category for all 3 hematopathologists. Factor analysis identified 3 independent factors likely to reflect underlying biologic processes. One factor related to overall and lineage-specific cellularity and was significantly associated with JAK2 V617F status (P < .001), a second factor related to megakaryocyte clustering, and a third was associated with the fibrotic process. No differences could be discerned between patients labeled as having "prefibrotic myelofibrosis" or "true ET" in clinical and laboratory features at presentation, JAK2 status, survival, thrombosis, major hemorrhage, or myelofibrotic transformation. These results show that histologic criteria described in the WHO classification are difficult to apply reproducibly and question the validity of distinguishing true ET from prefibrotic myelofibrosis on the basis of subjective morphologic criteria. This study was registered at http://isrctn.org as #72251782 and at http://eudract.emea.europa.eu/ as #2004-000245-38.
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PMID:Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. 1788 79

Philadelphia chromosome-negative myeloproliferative neoplasms include primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET). Although these 3 entities share many pathogenic characteristics, such as dysregulated Janus kinase (JAK)/signal transducer and activator of transcription signaling, they differ substantially regarding prognosis, progression to myelofibrosis (MF), risk of leukemic transformation, and specific medical needs. Accurate diagnosis and classification of myeloproliferative neoplasms are prerequisites for appropriate risk-based therapy and should be based on an integrated approach following the World Health Organization guidelines that, in addition to clinical, molecular, and cytogenetic evaluation, includes the examination of bone marrow morphology. Reticulin fibrosis at presentation in ET and PV is associated with increased risk of myelofibrotic transformation, and higher fibrosis grade in patients with MF is associated with worse prognosis. Additional assessment of collagen deposition and osteosclerosis may further increase diagnostic and prognostic precision. Moreover, the evaluation of bone marrow pathology has become very important in the new era of disease-modifying agents. In randomized controlled phase 3 studies, the JAK1/JAK2 inhibitor ruxolitinib provided rapid and lasting improvement in MF-related splenomegaly and symptom burden as well as a survival advantage compared with placebo or best available therapy. Follow-up for up to 5 years of patients who participated in a phase 1/2 study of ruxolitinib, revealed stabilization or reversal of bone marrow fibrosis in a proportion of patients with MF. Combinations of JAK inhibitors with other therapies, including agents with antifibrotic and/or anti-inflammatory properties, may possibly decrease bone marrow fibrosis further and favorably influence clinical outcomes.
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PMID:Impact of bone marrow pathology on the clinical management of Philadelphia chromosome-negative myeloproliferative neoplasms. 2551 54