Abstract：
:Myelofibrosis (MF; primary or post-essential thrombocythemia/polycythemia vera) is incurable clonal myeloproliferative disorder, with no effective treatment. Epigenetic changes play an important role in cancer pathogenesis through transcriptional silencing of critical tumor suppressor genes. We conducted a phase-II study to evaluate the activity of DNA methyltransferase inhibitor, 5-azacitidine, in patients with MF. Thirty-four patients (76% previously treated) received 5-azacitidine at 75 mg/m(2) subcutaneously daily for 7 days, every 4 weeks. Twelve (35%) patients had abnormal cytogenetics and 19 (70%) of 27 evaluable patients had JAK2(V617F) mutation. Responses occurred in 8 (24%) patients after a median of 5 months (range, 3-10). Partial response occurred in 1 (3%) patient (duration 22+ months) and clinical improvement in 7 (21%) patients (median duration 4 months; range, 2-8.5). Myelosuppression was the major adverse effect, with grade 3-4 neutropenia in 10 (29%) patients. Global DNA methylation assessed by the long interspersed nucleotide element (LINE) bisulfite/pyrosequencing assay decreased from 53% pretherapy to 44% on day 14 (P=0.0014) and returned to 50% at the end of the first 28-day cycle (P=0.016). 5-azacitidine is relatively well tolerated and results in induction of global hypomethylation in patients with MF, but results in limited clinical activity.
journal_name
Leukemiajournal_title
Leukemiaauthors
Quintás-Cardama A,Tong W,Kantarjian H,Thomas D,Ravandi F,Kornblau S,Manshouri T,Cortes JE,Garcia-Manero G,Verstovsek Sdoi
10.1038/leu.2008.91subject
Has Abstractpub_date
2008-05-01 00:00:00pages
965-70issue
5eissn
0887-6924issn
1476-5551pii
leu200891journal_volume
22pub_type
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