Myeloproliferative Neoplasms Transcriptome Reveals Pro-Inflammatory Signature and Enrichment in Peripheral Blood Monocyte-Related Genes.

Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients' peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients' transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN.

Neutropenia associated with myelofibrosis in systemic lupus erythematosus.

Although myelofibrosis has been described in systemic lupus erythematosus (SLE), this coexistence must be rare since there are few reports showing this combination. The possible relationship between hematologic abnormalities and SLE remains unresolved. The authors describe a 39-year-old woman with persistent neutropenia and SLE in whom myelofibrosis was found. Unlike previously reported cases, myelofibrosis did not resolve with steroid therapy. In this report, the clinical course of the patient is compared with others described in the literature.

Polycythemia vera and myelofibrosis: correlation of MR imaging, clinical, and laboratory findings.

Magnetic resonance (MR) imaging was performed in 14 patients with biopsy-proved polycythemia vera (n = 4) or myelofibrosis (n = 10) to determine whether MR imaging findings can be correlated with the clinicopathologic diagnosis and established clinical parameters of severity (serum lactate dehydrogenase [LDH] and cholesterol levels) and chronicity (spleen size). Evaluation of marrow in the proximal femurs showed that patients could be categorized into three distinct groups based on anatomic patterns of normal fatty and abnormal low-signal-intensity (non-fatty) marrow in the femoral capital epiphysis (FCE) and greater trochanter (GT). Patients with nonfatty marrow in both the FCE and GT (n = 8) had significantly higher serum LDH (P less than .02) and lower serum cholesterol (P less than .02) levels than patients with fatty marrow in at least the GT (n = 6). Splenic volume, as measured from MR images, was significantly greater in the myelofibrosis group than in the polycythemia vera group (P less than .001). MR imaging provided a better understanding of these hematologic disorders and novel parameters for classification that are different from conventional histologic and laboratory data.

Mielofibrose idiopática / Idiopathic myoelofibrosis

Os autores fazem uma revisäo bibliográfica recente e comparam os dados obtidos aos de prontuários médicos do Serviço de Hematologia do Hospital Brigadeiro - Säo Paulo, no período de 1983 a 1988. Foram analisados oito casos de mielofibrose idiopática (MFI), confirmados através de biópsia óssea de crista ilíaca posterior com agulha de Jamshidi. A faixa etária preodminante foi de 51 a 60 anos, sendo cinco pacientes do sexo masculino e três do sexo feminino. Os sintomas mais referidos foram adinamia, fraqueza e sangramento (seis-oito casos), emagrecimento e dores ósseas (quatro-oito casos). Os sinais encontrados com maior freqüência foram explenomegalia e anemia (sete-oito casos), hepatomegalia (cinco-oito casos) e icterícia (dois-oito casos). O hematoma näo apresentou padräo definido. A maior parte dos casos foram diagnosticados em estádios avançados da doença. O tratamento isolado ou combinado com bussulfan, prednisona, oximetalona e radioterapia esplênica mostrou-se útil para alívio de sintomas abdominais compressivos. A análise retrospectiva dos pacientes con MFI demonstra que essa patologia deve ser obrigatoriamente incluída no diagnóstico diferencial de hepatoesplenomegalia associada a anemia

[Idiopathic myelofibrosis]. / Mielofibrose idiopática.

The authors make a review of recent data in the literature and compare them to their own cases between 1983 and 1988. They analyzed eight patients with idiopathic myelofibrosis confirmed with bone marrow biopsy of the posterior iliac wrist with Jamshidi's needle. Most patients were between 55 and 60 years old (5 male and 3 female). Major symptoms were weakness and bleeding (6/8 cases), weight loss and bone distress (4/8 cases). In general, physical signs were splenomegaly and anemia (7/8 cases), hepatomegaly (5/8 cases), and jaundice (2/8 cases). Laboratory features were variable. Most cases were diagnosed in an advanced stage of the disease. Therapy with busulfan, prednisone, oxymetholone and radiotherapy of the spleen was used alone or in combination to relieve compressive abdominal symptoms. This review shows that idiopathic myelofibrosis should be included in the differential diagnosis of patients with hepatosplenomegaly and anemia.

Vitamin D-deficiency rickets and myelofibrosis.

This study was aimed at detecting the early appearance of myelofibrosis by bone marrow biopsy examination in children with vitamin D-deficiency rickets. Twelve children, aged 4 to 18 months, were evaluated. Only a minimal increase of the reticulin was shown in rachitic children without anemia in whom no other laboratory evidence of myelofibrosis was present. Early signs of myelofibrosis with increase of reticulin were present in rachitic infants with anemia. In patients of the same age with iron deficiency anemia, the bone marrow reticulin findings were normal. Bone marrow biopsy after successful treatment of rickets could be repeated in one patient with myelofibrosis; results indicated that the myelofibrosis with anemia associated with vitamin D-deficiency rickets is reversible by vitamin D treatment.

Intraplatelet levels of vWF:Ag and fibrinogen in myeloproliferative disorders.

Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.

Myelofibrosis in children with chronic renal insufficiency.

During investigation of splenomegaly in a boy with chronic renal failure and osteodystrophy, bone marrow aspirates resulted in "dry taps," whereas biopsied material provided evidence that the marrow had been replaced by fibrous tissue. In a study of six other children with chronic renal failure, similar changes were observed. These findings suggest that the anemia of chronic renal failure may in part be a result of myelofibrosis, and the resulting reduction of functional bone marrow may limit the tolerance to immunosuppressive agents in patients who undergo renal transplantation.