Treatment of myelodysplastic syndrome with a DNA methyltransferase inhibitor: lack of evidence for induction of chromosomal instability.
In several large phase II trials, low-dose treatment with the azanucleoside 5-aza-2'-deoxycytidine (decitabine, DAC) resulted in complete hematologic and cytogenetic responses in 23 and 31% of MDS patients, respectively. The question of induction of chromosomal instability by this demethylating agent was addressed by serial karyotypic analyses. 53/122 DAC-treated patients had all normal metaphases at time of treatment start. In 46/53 patients, sequential cytogenetic analyses were performed. 9/46 patients (20%) acquired clonal chromosomal abnormalities during follow-up (4/9 transient). 8/9 abnormalities were gains or losses of entire chromosomes. The rate and pattern of cytogenetic evolution are thus not higher than in historical MDS cohorts not receiving specific treatment.
Haas
Peter S
PS
Department of Medicine, Division of Hematology/Oncology, University of Freiburg Medical Center, Hugstetter Str. 55, D-79106 Freiburg, Germany.
Wijermans
Pierre
P
Verhoef
Gregor
G
Lübbert
Michael
M
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D043171:Chromosomal Instability / Q000187:drug effects*; D002872:Chromosome Deletion; D020732:Cytogenetic Analysis; D000077209:Decitabine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008677:Metaphase / Q000187:drug effects; D008875:Middle Aged; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine