Abstract
Leukemic blast cells taken from 83 patients with AML at time of diagnosis and 20 patients during follow-up in complete remission were examined for the expression of wt-1 mRNA. For this purpose blast cells were isolated from bone marrow or peripheral blood and total RNA was extracted. The wt-1 transcription was subsequently studied via RT-PCR. Mononuclear cells and bone marrow from healthy persons were used as controls. Wilms’ tumor mRNA was detectable in 67 out of 83 cases of AML (81%). None of the 13 healthy controls expressed wt-1. After achieving cytological Complete Remission (CR) 14/20 patients studied lost wt-1 expression. In 7/8 patients in CR persistence or reappearance of wt-1 expression preceded relapse of the disease. Response to therapy and survival did not correlate with wt-1 mRNA expression in newly diagnosed AML before therapy. Our data show that expression of wt-1 mRNA is widely spread in AML and may be a useful marker for detection of minimal residual disease (MRD) in acute leukemia. The follow-up data strongly suggest that analysis of wt-1 gene expression via PCR in CR may be a sensitive technique for the early detection of relapse. Analysis of wt-1 expression accompanying routine bone marrow aspiration may be useful to define the quality of remission and early prediction of relapse of the disease. Its relevance to outcome, follow-up, and detection of MRD, however, as well as its potential role in the pathogenesis of acute leukemia, remain to be confirmed by ongoing studies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Maseki N, Miyoshi H, Shimizu K, Homma C, Ohki M, Sakurai M, Kaneko Y. The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1. Blood 1993; 81: 1573–1579.
van Dongen JJM, Breit TM, Adriaansen HJ, Beishuizen A, Hooijkaas H. Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction. Leukemia 1992; Suppl 1: 47–59.
Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 1990; 60: 509–520.
Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GAP. Homozygous deletion in Wilms’ tumor of a zinc-finger gene identified by chromosome jumping. Nature 1990; 343: 774–778.
Brieger J., Weidmann E., Fenchel K., Mitrou P.S., Hoelzer D., Bergmann L: The expression of the Wilms’ tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells. Leukemia 1994; 8: 2138–2143.
Brieger J., Bergmann L., Weidmann E., Maurer U., Hoelzer D., Mitrou P.S.: The Wilms’ tumor gene (WT-1) is frequently expressed in acute leukemias and may provide sensitive detection of residual blast cells by PCR. Ann. Oncol. (1995), in press
Drummond IA, Madden SL, Rohwer-Nutter P, Bell GI, Sukhatme VP, Rauscher FJ 3d. Repression of the insulin-like growth factor II gene by the Wilms’ tumor suppressor wt-1. Science 1992; 257: 674–678.
Gashler AL, Bonthron DT, Madden SL, Rauscher FJ 3d, Collins T, Sukhatme VP. Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1. PNAS 1992; 89: 10984–10988.
Dey BR, Sukhatme VP, Roberts AB, Sporn MB, Rauscher FJ, KIM SJ: Repression of the transforming growth factor-beta 1 gene by the Wilms’ tumor suppressor WT1 gene product. Mol Endocrinol 1994; 8: 595–602.
Sukhatme VP, Cao X, Chang LC, Tasi-Moris C-H, Stamenkovich D, Ferreira PCP, Cohen DR, Edwards SA, Shows TB, Curran T, Le Beau MM, Adamson ED. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 1988; 53:37–43.
Joseph LJ, Le Beau MM, Jamieson GA, Acharys S, Shows TB, Rowley JD, Sukhatme VP. Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with ‘zinc-binding finger’ structure. PNAS 1988; 85: 7164–7168.
Madden SL, Cook DM, Morris JF, Gashler A, Sukhatme VP, Rauscher FJ III. Transcriptional repression mediated by the WT-1 Wilms’ tumor gene product. Science 1991; 253: 1550–1553.
Wang ZY, Qiu QQ, Deuel TF. The Wilms’ tumor gene product wt-1 activates or suppresses transcription through separate functional domains. J Biol Chem 1993; 268(13) 9172–9175.
Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE. An internal deletion within an 11pl3 zinc finger gene contributes to the development of Wilms’ tumor. Cell 1990; 61: 1257–1269.
Coppes MJ, Liefers GJ, Paul P, Yeger H, Williams BR. Homozygous somatic wt-1 point mutations in sporadic unilateral Wilms tumor. PNAS 1993; 90: 1416–1419.
Miwa H, Beran M, Saunders GF. Expression of the Wilms’ tumor gene (wt-1) in human leukemias. Leukemia 1992; 6: 405–409.
Tatsushi M, Ahuja H, Kubota T, Kubonishi I, Koeffler HP, Miyoshi I. Expression of the Wilms’ tumor gene, wt-1, in human leukemia cells. Leukemia 1993; 7: 970–977.
Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Br J Haematol 1976; 33: 451–458.
Brenner B, Wildhardt G, Schneider S, Royer-Pokora B. RNA polymerase chain reaction detects different levels of four alternatively spliced wt-1 transcripts in Wilms’ tumors. Oncogene 1992; 7:1431–1433.
Lukens JN. Classification and differentiation of the acute leukemias. In Clinical Hematology (Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN; eds) Lea & F ebiger, Philadelphia, 1993, pp 1873–1919.
Bergmann L., Heil G., Kolbe K., Lengfelder E., Puzicha E., Martin H., Lohmeyer J., Mitrou P.S., Hoelzer D.: Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myelocytic leukemia. Leuk. Lymphoma 1995, 16: 271–279.
Jahn B., Bergmann L., Weidmann E., Brieger J., Fenchel K., Schwulera U., Hoelzer D., Mitrou P.S.. Bone marrow derived T cell clones of previously untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity. Leuk Res 1995, 19: 73–82.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Brieger, J., Weidmann, E., Maurer, U., Mitrou, P.S., Hoelzer, D., Bergmann, L. (1997). Detection of the Wilms Tumor Gene (wt-1) mRNA in Complete Remission of AML Frequently Precedes Relapse. In: Büchner, T., Schellong, G., Ritter, J., Creutzig, U., Hiddemann, W., Wörmann, B. (eds) Acute Leukemias VI. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60377-8_21
Download citation
DOI: https://doi.org/10.1007/978-3-642-60377-8_21
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64379-8
Online ISBN: 978-3-642-60377-8
eBook Packages: Springer Book Archive