BACKGROUND: JAK2V617F occurs in approximately 50% of patients with essential thrombocythemia (ET). Qualitative studies of mutation analysis have previously reported an association between JAK2V617F and advanced age, higher hemoglobin level, higher leukocyte count, and lower platelet count. A possible association with thrombotic complication has also been considered. METHODS: Allele-specific, quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed in 176 patients with ET using genomic DNA from archived bone marrow, which was collected within 1 year (n=72 patients), between 1 and 5 years (n=64 patients), or after 5 years (n=40 patients) of diagnosis. RESULTS: JAK2V617F was detected in 96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median, 6.3%). Neither mutational frequency (P=.37) nor mutant allele burden (P=.62) was affected by the timing of bone marrow sample collection. The presence of JAK2V617F was found to be significantly associated with higher hemoglobin level (P<.0001), lower platelet count (P=.001), higher leukocyte count (P=.008), increased incidence of venous thrombosis occurring after diagnosis (P=.02), and older age at diagnosis (P=.03). All but age retained significance in multivariable analysis. In mutation-positive patients (n=96 patients), JAK2V617F allele burden clustered between 1% and 22% in 94 cases, in whom it correlated directly and significantly with platelet and leukocyte counts, palpable splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The latter 2 associations remained significant with the inclusion of the remaining 2 outlier cases with 100% mutant allele burden; in addition, an association with male gender became evident. CONCLUSIONS: JAK2V617F allele burden imparts additional phenotypic effects in ET. (c) 2007 American Cancer Society.
BACKGROUND: JAK2V617F occurs in approximately 50% of patients with essential thrombocythemia (ET). Qualitative studies of mutation analysis have previously reported an association between JAK2V617F and advanced age, higher hemoglobin level, higher leukocyte count, and lower platelet count. A possible association with thrombotic complication has also been considered. METHODS: Allele-specific, quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed in 176 patients with ET using genomic DNA from archived bone marrow, which was collected within 1 year (n=72 patients), between 1 and 5 years (n=64 patients), or after 5 years (n=40 patients) of diagnosis. RESULTS: JAK2V617F was detected in 96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median, 6.3%). Neither mutational frequency (P=.37) nor mutant allele burden (P=.62) was affected by the timing of bone marrow sample collection. The presence of JAK2V617F was found to be significantly associated with higher hemoglobin level (P<.0001), lower platelet count (P=.001), higher leukocyte count (P=.008), increased incidence of venous thrombosis occurring after diagnosis (P=.02), and older age at diagnosis (P=.03). All but age retained significance in multivariable analysis. In mutation-positive patients (n=96 patients), JAK2V617F allele burden clustered between 1% and 22% in 94 cases, in whom it correlated directly and significantly with platelet and leukocyte counts, palpable splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The latter 2 associations remained significant with the inclusion of the remaining 2 outlier cases with 100% mutant allele burden; in addition, an association with male gender became evident. CONCLUSIONS: JAK2V617F allele burden imparts additional phenotypic effects in ET. (c) 2007 American Cancer Society.
Authors: Brady L Stein; Stephen T Oh; Dmitriy Berenzon; Gabriela S Hobbs; Marina Kremyanskaya; Raajit K Rampal; Camille N Abboud; Kenneth Adler; Mark L Heaney; Elias J Jabbour; Rami S Komrokji; Alison R Moliterno; Ellen K Ritchie; Lawrence Rice; John Mascarenhas; Ronald Hoffman Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544
Authors: Holly L Geyer; Heidi Kosiorek; Amylou C Dueck; Robyn Scherber; Stefanie Slot; Sonja Zweegman; Peter Aw Te Boekhorst; Zhenya Senyak; Harry C Schouten; Federico Sackmann; Ana Kerguelen Fuentes; Dolores Hernández-Maraver; Heike L Pahl; Martin Griesshammer; Frank Stegelmann; Konstanze Döhner; Thomas Lehmann; Karin Bonatz; Andreas Reiter; Francoise Boyer; Gabriel Etienne; Jean-Christophe Ianotto; Dana Ranta; Lydia Roy; Jean-Yves Cahn; Claire N Harrison; Deepti Radia; Pablo Muxi; Norman Maldonado; Carlos Besses; Francisco Cervantes; Peter L Johansson; Tiziano Barbui; Giovanni Barosi; Alessandro M Vannucchi; Chiara Paoli; Francesco Passamonti; Bjorn Andreasson; Maria L Ferrari; Alessandro Rambaldi; Jan Samuelsson; Keith Cannon; Gunnar Birgegard; Zhijian Xiao; Zefeng Xu; Yue Zhang; Xiujuan Sun; Junqing Xu; Jean-Jacques Kiladjian; Peihong Zhang; Robert Peter Gale; Ruben A Mesa Journal: Haematologica Date: 2016-08-18 Impact factor: 9.941