Leukemia risk models in primary myelofibrosis: an International Working Group study

Division of Hematology, Rochester, MN, USA.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.43). 01/2012; 26(6):1439-41. DOI: 10.1038/leu.2011.374
Source: PubMed


Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

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Available from: Arturo Pereira, Apr 08, 2014
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    • "In 15–20% of patients the disease evolves into an aggressive form of acute leukaemia. Variables associated with leukaemia transformation are peripheral blood blasts >2%, thrombocytopenia, and highrisk karyotypic abnormalities (Tefferi et al, 2012). The molecular mechanisms underlying the leukaemic transformation are still poorly characterized. "
    British Journal of Haematology 08/2013; 162(3). DOI:10.1111/bjh.12376 · 4.71 Impact Factor
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    • "Collectively, the results of this paper are in favor of a two routes model of BT in PMF, in which oncogenic events provide a leukemogenic potential both to JAK2V617F wt clone and to the JAK2V617F mutated clone with a homozygous genotype. These results re-open the issue of prognostic indicators for BT in PMF [36], and should be considered in the light of the current therapeutic strategies for PMF. The possibility to functionally reduce the JAK2V617F activity with new anti-JAK2 agents [37] questions whether these therapies, when applied in patients with high JAK2V617F allele burden, could prevent the evolution toward BT. "
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    ABSTRACT: The influence of JAK2 V617F mutation on blast transformation (BT) and overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large cohort of patients we applied competing risks analysis for studying the influence of JAK2V617F mutation on BT in PMF. In 462 PMF-fibrotic type patients (bone marrow [BM] fibrosis grade >0) we computed the incidence of BT and death in the framework of Cox regression analysis and of Fine and Gray competing risks analysis for BT. At the Cox regression analysis, having either a wild-type (wt) or a homozygous JAK2V617F genotype were factors for BT (HR, 1.98 and 2.04, respectively, with respect to the heterozygous genotype), but not for OS. At the competing risks regression analysis, the risk for BT in wt and homozygous V617F patients increased with respect to Cox analysis, giving a sHR of 2.17 and 2.12, respectively. Correcting the results for the variables that could have influence on BT, JAK2V617F wt and homozygous genotypes remained independently associated with BT. In a validation cohort of 133 independent cases with PMF-prefibrotic type (BM fibrosis grade = 0), the BT predictive model including JAK2V617F genotype and older age retained high discriminant capacity (C statistics, 0.70; 95% CI, 0.47 to 0.92). The accumulation of mutated alleles in the JAK2V617F clone or the selective acquisition of a proliferative advantage in the wt clone are two relevant routes to BT in PMF. The influence of these results on treatment decisions with anti-JAK2 agents should be tested.
    PLoS ONE 03/2013; 8(3):e59791. DOI:10.1371/journal.pone.0059791 · 3.23 Impact Factor
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    • "Treatment of patients with myelofibrosis should be individualized based on DIPSS prognostic score and symptomatology [90] (Figures 3A, 3B). HCT should be considered for eligible patients with a DIPSS score of Int-2 or High-risk, or Int-1 risk patients who are transfusiondependent or have a high risk of leukemic transformation. "
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    ABSTRACT: Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias, splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory cytokines. MF is associated with decreased survival. The quality of life of patients with MF is similar to other advanced malignancies. Allogeneic hematopoietic cell transplantation is a curative treatment, but is applicable to a minority of patients with MF. None of the conventional therapies are known to alter the natural history of the disease. Significant progress has been made in the last few years in the understanding of disease biology of MF. Discovery of the JAK2V617F mutation paved the way for drug discovery in MF, and the first JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada. Several other JAK1/2 inhibitors are at various stages of clinical development. As a consequence, the therapeutic landscape of MF is changing from a disease where no effective therapies existed to one with several novel treatment options on the horizon. In this report, we assess the changing therapeutic options for MF, and critically analyze the position of novel treatments in the current armamentarium.
    American Journal of Blood Research 11/2012; 2(3):170-86.
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