Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients.
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.
Mavrogianni
Despina
D
First Department of Internal Medicine, Laikon General Hospital, University of Athens, Greece.
Viniou
Nora
N
Michali
Evi
E
Terpos
Evangelos
E
Meletis
John
J
Vaiopoulos
George
G
Madzourani
Marina
M
Pangalis
Gerasimos
G
Yataganas
Xenophon
X
Loukopoulos
Dimitris
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics* / Q000502:physiology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics* / Q000502:physiology; D005260:Female; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007938:Leukemia / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D013922:Thrombocytosis / Q000150:complications* / Q000188:drug therapy / Q000235:genetics
D006918:Hydroxyurea