Correlation between lower c-mpl protein expression and favorable cytogenetic groups in acute myeloid leukemia

The gene for the thrombopoietin receptor, c-mpl, has been shown to be overe xpressed at the mRNA level in acute myeloid leukemia (AML) and myelodysplas tic syndrome. A recent study reported c-mpl mRNA overexpression in 60% of a small sample of AML patients, and this overexpression correlates with shor ter complete remission but not with karyotype group. We quantified c-mpl pr otein expression in 107 cases of AML and 24 normal bone marrow and 12 norma l peripheral blood samples by using Western blot analysis and radioimmunoas say (RIA). Western blot analysis revealed no detectable level of c-mpl prot ein in the normal samples, whereas trace amounts were detected by RIA. c-mp l protein expression was increased (greater than or equal to twice normal) in 65% of the AML cases. c-mpl protein expression was correlated with cytog enetic groups (P = 0.0009, Kruskal-Wallis test in rejecting the hypothesis that c-mpl expression was the same in different groups). Specifically, pati ents with favorable cytogenetic groups (t(8;21), inv16, and t(15;17)) had l ower c-mpl protein expression (median 1.7 times normal), whereas patients w ith unfavorable abnormalities (+8, -5 or -7, and del(ll)(q23)) and normal c ytogenetics had high expression (3.1 and 2.85 times normal, respectively). The findings were the same when only the 61 untreated AML patients were con sidered. No statistically significant correlation between c-mpl expression and age or antecedent hematologic disorder was found. These results suggest that c-mpl protein overexpression in AML may play a role in the aggressive ness of this disease. (C) 1998 Elsevier Science Ltd. All rights reserved.