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.
OBJECTIVE
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).


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).


CONCLUSIONS
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.
Wetzler
M
M
Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. wetzler@dm3100.med.buffalo.edu
Baer
M R
MR
Bernstein
S H
SH
Blumenson
L
L
Stewart
C
C
Barcos
M
M
Mrózek
K
K
Block
A W
AW
Herzig
G P
GP
Bloomfield
C D
CD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D016019:Survival Analysis; D016896:Treatment Outcome
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human