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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2703-2707
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Negative prognostic value of glutathione S-transferase
(GSTM1 and GSTT1) deletions in adult
acute myeloid leukemia
Maria Teresa Voso,
Francesco D'Alo',
Rossana Putzulu,
Luca Mele,
Alessandra Scardocci,
Patrizia Chiusolo,
Roberto Latagliata,
Francesco Lo-Coco,
Sergio Rutella,
Livio Pagano,
Stefan Hohaus, and
Giuseppe Leone
From the Istituto di Ematologia, Universita' Cattolica
S. Cuore and Dipartmento di Biotecnologie Cellulari ed Ematologia,
Universita' La Sapienza, Rome, Italy.
Glutathione S-transferases (GSTs) are enzymes involved in the
detoxification of several environmental mutagens, carcinogens, and
anticancer drugs. GST polymorphisms resulting in decreased enzymatic
activity have been associated with several types of solid tumors. We
determined the prognostic significance of the deletion of 2 GST
subfamilies genes, M1 and T1, in patients with acute myeloid
leukemia (AML). Using polymerase chain reactions, we analyzed the
GSTM1 and GSTT1 genotype in 106 patients with AML (median age, 60.5 years; range, 19-76 years). The relevance of
GSTM1 and GSTT1 homozygous deletions was
studied with respect to patient characteristics, response to therapy,
and survival. Homozygous deletions resulting in null genotypes at the
GSTM1 and GSTT1 loci were detected in 45 (42%)
and 30 (28%) patients, respectively. The double-null genotype was
present in 19 patients (18%). GST deletions predicted poor response to
chemotherapy (P = .04) and shorter survival
(P = .04). The presence of at least one GST deletion
proved to be an independent prognostic risk factor for response to
induction treatment and overall survival in a multivariate analysis
including age and karyotype (P = .02). GST genotyping was
of particular prognostic value in the cytogenetically defined
intermediate-risk group (P = .003). In conclusion,
individuals with GSTM1 or GSTT1 deletions (or
deletions of both) may have an enhanced resistance to chemotherapy and
a shorter survival.
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