Home About us Contact
|
Home About us Contact | ||
|
|
||
Primary Myelofibrosis (primary + myelofibrosis)
Selected AbstractsChromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype,phenotype associationsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Domenica Caramazza Abstract Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype,phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL -negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12,1q32 in PV, 1q21,32,1q32,44 in post-PV MF or PMF), deletions (e.g. 1p13,36,pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21,25;p21.3,23), and other partner chromosomes involving 1q10/1p11 and 1q21,25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21,1q32 and 1p11,13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. [source] Prognostic relevance of cytogenetic abnormalities in primary myelofibrosis: comparison of recent reports from Japan, the Mayo Clinic and MD Anderson Cancer CenterEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2009Ayalew Tefferi No abstract is available for this article. [source] Familial chronic myeloproliferative disorders: the state of the art,HEMATOLOGICAL ONCOLOGY, Issue 3 2008Elisa Rumi Abstract Familial chronic myeloproliferative disorders are defined when in the same pedigree at least two relatives have a chronic myeloproliferative disorder (CMD) as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). This condition should be distinguished from inherited disorders with Mendelian transmission and single haematopoietic lineage proliferation, named hereditary erythrocytosis and thrombocytosis. The recently discovered mutations in patients with CMD (V617F and exon 12 of JAK2 gene, MPL gene), and those identified in hereditary erythrocytosis and in hereditary thrombocytosis have improved our ability to discriminate these conditions. In familial CMD, the JAK2 mutations are acquired and occur as secondary genetic events. As both mutations of the JAK2 gene have been reported in the same pedigree, a genetic predisposition to the acquisition of the JAK2 mutations is supposed to be inherited. The prevalence of familial cases within CMD is at least 7.6%. The inheritance pattern of familial CMD is consistent with an autosomal dominant trait with decreased penetrance. The clinical presentation at diagnosis of patients with familial CMD does not differ from that of patients with sporadic CMD. In addition, patients with familial CMD develop the same type of complications (thrombosis and haemorrhage) and disease evolution (post-PV myelofibrosis, post-ET myelofibrosis and leukaemia) observed in patients with sporadic CMD. The 10-year survival is 83% for patients with familial PV, 100% for those with familial ET, and 30% for those with familial PMF. The aim of this review is to focus the state of the art of familial CMD and to offer an overview of inherited conditions causing erythrocytosis and thrombocytosis. Copyright © 2008 John Wiley & Sons, Ltd. [source] The analysis of JAK2 and MPL mutations and JAK2 single nucleotide polymorphisms in MPN patients by MassARRAY assayINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2010S.-J. ZHANG Summary Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN). Allele-Specific Polymerase Chain Reaction (AS-PCR), direct sequencing and MassARRAY assay were used to ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients. The positive rate of JAK2 V617F in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% respectively. One ET patient and two PMF patients harboured the MPL W515L mutation and three PV patients harboured JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Clinical data demonstrated that PV patients with JAK2 exon 12 mutations were younger, had higher haemoglobin levels and white blood cell counts than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype also was not significantly different among PV, ET and PMF patients. We conclude that JAK2 V617F is a major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients. [source] Recovery of normal autologous myelopoiesis after graft rejection following allogeneic bone marrow transplant for agnogenic myeloid metaplasiaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2006S. ALKINDI Summary Allogeneic hematopoietic transplantation is the only currently available therapy that has the potential to cure agnogenic myeloid metaplasia (AMM) or primary myelofibrosis (PMF). Amelioration of fibrosis and eradication of the abnormal clone is thought to occur through the repopulation of marrow by donor-derived hematopoiesis and graft- vs. -host reaction leading to graft vs. tumor effect. We report here a 50-year-old female with AMM/PMF, conditioned with busulfan and cyclophosphamide, who rejected a single locus (HLA-B) mismatched bone marrow transplant from her daughter, but recovered normal autologous hematopoiesis with disappearance of marrow fibrosis and extramedullary hematopoiesis. Variable number tandem repeats (VNTR) analysis showed a gradual loss of donor-derived hematopoietic cells with recovery of autologous hematopoiesis. This case therefore illustrates that eradication of AMM/PMF in this patient with myeloablative chemotherapy combined with a transient allogeneic effect was sufficient to suppress the abnormal stem cell clone associated with AMM/PMF with subsequent cure. [source] CXCR4-independent rescue of the myeloproliferative defect of the gata1low myelofibrosis mouse model by Aplidin®,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Maria Verrucci The discovery of JAK2 mutations in Philadelphia-negative myeloproliferative neoplasms has prompted investigators to evaluate mutation-targeted treatments to restore hematopoietic cell functions in these diseases. However, the results of the first clinical trials with JAK2 inhibitors are not as promising as expected, prompting a search for additional drugable targets to treat these disorders. In this paper, we used the hypomorphic Gata1low mouse model of primary myelofibrosis (PMF), the most severe of these neoplasms, to test the hypothesis that defective marrow hemopoiesis and development of extramedullary hematopoiesis in myelofibrosis is due to insufficient p27Kip1 activity and is treatable by Aplidin®, a cyclic depsipeptide that activates p27Kip1 in several cancer cells. Aplidin® restored expression of Gata1 and p27Kip1 in Gata1low hematopoietic cells, proliferation of marrow progenitor cells in vitro and maturation of megakaryocytes in vivo (reducing TGF-,/VEGF levels released in the microenvironment by immature Gata1low megakaryocytes). Microvessel density, fibrosis, bone growth, and marrow cellularity were normal in Aplidin®-treated mice and extramedullary hematopoiesis did not develop in liver although CXCR4 expression in Gata1low progenitor cells remained low. These results indicate that Aplidin® effectively alters the natural history of myelofibrosis in Gata1low mice and suggest this drug as candidate for clinical evaluation in PMF. J. Cell. Physiol. 225: 490,499, 2010. © 2010 Wiley-Liss, Inc. [source] Prognosis and survivorship in primary myelofibrosis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010John T. Reilly No abstract is available for this article. [source] Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis,prognostic relevance is independent of IPSS or karyotype,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Ayalew Tefferi The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients (,24%) required transfusions at diagnosis whereas 22 (,9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Prodromal myeloproliferative neoplasms: The 2008 WHO classification,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Hans Michael Kvasnicka The concept of prodromal chronic myeloproliferative neoplasms has been endorsed by the WHO classification implicating a stepwise evolution of disease. Histology of the bone marrow (BM) and borderline to mildly expressed clinical features play a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By lowering the platelet count for essential thrombocythemia and regarding BM morphology, early manifestations are tackled. Pre-polycythemic stages of polycythemia vera with a low hemoglobin level at onset are diagnosed by positive JAK2V617F mutation status, a low erythropoietin value, and characteristic BM features. The revised WHO classification incorporates hematological, morphological, and moleculargenetic parameters to generate a consensus-based working diagnosis. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Red blood cell transfusion need at diagnosis adversely affects survival in primary myelofibrosis,increased serum ferritin or transfusion load does not,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Ayalew Tefferi Serum ferritin level at diagnosis was available in 185 patients with primary myelofibrosis (PMF); twenty-two (12%) patients had serum ferritin >1,000 ng/mL and 32 (17%) were red blood cell (RBC) transfusion-dependent. As expected, RBC transfusion need and increased serum ferritin displayed strong correlation (P < 0.0001); in addition, the latter but not the former correlated with advanced age (P < 0.0001). During median follow-up of 28 months (range 0.5,231), peak serum ferritin levels exceeded 1,000 ng/mL in 41 (22%) patients. On multivariable analysis that included age as a covariate, RBC transfusion need at diagnosis (P < 0.0001), but not increased serum ferritin or transfusion load, predicted shortened survival. The prognostic relevance of RBC transfusion need was independent of the International Prognostic Scoring System and was also illustrated for leukemia-free survival (P = 0.003). In PMF, the presence of a more severe erythropoietic defect, and not iron overload, has additional adverse prognostic value. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Survival in young patients with intermediate-/high-risk myelofibrosis: Estimates derived from databases for non transplant patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Sergio Siragusa Recent studies have suggested that allogenic stem cell transplantation (allo-SCT) might be a better treatment option, compared to drug therapy, for young patients with high-/intermediate-risk primary myelofibrosis (PMF). However, there are no controlled studies that validate this contention and allo-SCT is associated with a substantial risk of procedure-related mortality and morbidity. In a retrospective analysis of nontransplant PMF patients, who were both young (age <60 years) and with high-/intermediate-risk disease, 1- and 3-year survival estimates were 87% and 55%, 95% and 77%, 71% and 58%, respectively, involving patients seen at three different centers with expertise in PMF; these data did not appear to be inferior to those published in the context of either myeloablative or reduced-intensity conditioning allo-SCT. These observations underscore the need for controlled studies to accurately assess the value of allo-SCT in PMF. AM. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Blood film features of primary myelofibrosis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Barbara J. Bain No abstract is available for this article. [source] correspondence: Incidence of leukaemia in patients with primary myelofibrosis and RBC,transfusion-dependenceBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2010Francesco Passamonti No abstract is available for this article. [source] correspondence: Splenectomy after allogeneic haematopoietic stem cell transplantation in patients with primary myelofibrosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2010Marie Robin First page of article [source] | ||||||||||