Journal of Clinical Oncology, Vol 15, 2262-2268, Copyright © 1997 by American Society of Clinical Oncology
Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy
M Wetzler, MR Baer, SH Bernstein, L Blumenson, C Stewart, M Barcos, K Mrozek, AW Block, GP Herzig and CD Bloomfield
Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. wetzler@dm3100.med.buffalo.edu
PURPOSE: c-mpl, the human homolog of v-mpl, is the receptor for
thrombopoietin. Given that c-mpl expression carries an adverse prognosis in
myelodysplastic syndrome and given the prognostic significance of
expression of other growth factor receptors in other diseases, we attempted
to determine whether c-mp/mRNA expression is a prognostic factor in acute
myeloid leukemia (AML). PATIENTS AND METHODS: We analyzed bone marrow
samples from 45 newly diagnosed AML patients by reverse-transcription
polymerase chain reaction. RESULTS: Samples from 27 patients (60%)
expressed c-mpl mRNA (c-mpl+); their clinical and laboratory features were
compared with those of the 18 patients without detectable levels of
c-mpl(c-mpl-). No significant differences in age, sex, leukocyte count,
French-American-British subtype, or karyotype group were found. c-mpl+
patients more commonly had secondary AML (41% v 11%; P = .046) and more
commonly expressed CD34 (67% v 12%; P = .0004). There was no significant
difference in complete remission (CR) rate. However, c-mpl+ patients had
shorter CR durations (P = .008; median, 6.0 v > 17.0 months). This was
true when only de novo AML patients were considered and when controlling
for age, cytogenetics, or CD34 expression. There was a trend toward shorter
survival in c-mpl+ patients (P = .058; median, 7.8 v 9.0 months).
CONCLUSION: These data suggest that c-mpl expression is an adverse
prognostic factor for treatment outcome in adult AML that must be
considered in the analysis of clinical studies using thrombopoietin in AML.
