Prognostic significance of Wilms tumor 1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes
Abstract
BACKGROUND:
This present study was designed to follow up 82 patients among 115 MDS patients registered in study ODK-0801 for 5 years, to analyze the relationship between the WT1 mRNA expression level and prognosis.
OBJECTIVE:
This study aimed to investigate the clinical utility of WT1 mRNA expression levels.
METHODS:
After study ODK-0801, we investigated the conditions of the same patients once a year, including any clinical and laboratory findings supporting the diagnosis, and treatment among the living patients.
RESULTS:
When we assessed the survival time of 82 MDS patients by WT1 mRNA expression level, there were significant differences between the < 500 and ≥ 104 copies/μ g RNA groups and between the 500-104 and ≥ 104 copies/μ g RNA groups for BM levels (p < 0.01). Examination of the time of freedom from acute myeloid eukemia (AML) transformation indicated that a high WT1 mRNA expression level (> 104 copies/μ g RNA) was a strong prognostic factor for a short time to AML transformation.
CONCLUSION:
The results indicate that the tumorigenesis of MDS is likely to originate at the stem cell level, suggesting that the WT1 mRNA level measurement in the BM is an effective prognostic marker in patients with MDS.
References
[1] | Tamaki H., , Ogawa H., , Ohyashiki K., , Ohyashiki J.H., , Iwama H., , Inoue K., , Soma T., , Oka Y., , Tatekawa T., , Oji Y., , Tsuboi A., , Kim E.H., , Kawakami M., , Fuchigami K., , Tominaga M., , Toyama K., , Aozasa K., , Kishimoto T., and Sugiyama H., The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes, Leukemia 13: ((1999) ), 393-9. |
[2] | Cilloni D., , Gottardi E., , Messa F., , Fava M., , Scaravaglio P., , Bertini M., , Girotto M., , Marinone C., , Ferrero D., , Gallamini A., , Levis A., and Saglio G., Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System score in patients with myelodysplastic syndromes, J Clin Oncol 21: ((2003) ), 1988-95. |
[3] | Patmasiriwat P., , Fraizer G., , Kantarjian H., and Saunders G.F., WT1 and GATA1 expression in myelodysplastic syndrome and acute leukemia, Leukemia 13: ((1999) ), 891-900. |
[4] | Bader P., , Niemeyer C., , Weber G., , Coliva T., , Rossi V., , Kreyenberg H., , Gerecke A., and Biondi A., WT1 gene expression: Useful marker for minimal residual diseases in childhood myelodysplastic syndromes and juvenile myelo-monocytic leukemia, Eur J Haematol 73: ((2004) ), 25-8. |
[5] | Tamura K., , Kanazuwa T., , Suzuki M., , Koitabashi M., , Ogawa C., and Morikawa A., Successful rapid discontinuation of immunosuppressive therapy at molecular relapse after allogeneic bone marrow trasplantation in pediatric patients with myelodysplastic syndrome, Am J Hematol 81: ((2006) ), 139-41. |
[6] | Iwasaki T., , Sugisaki C., , Nagata K., , Takagi K., , Takagi A., , Kojima T., , Ito M., , Nakamura S., , Naoe T., and Murate T., Wilms' tumor 1 message and protein expression in bone marrow failure syndrome and acute leukemia, Pathol Int 57: ((2007) ), 645-51. |
[7] | Tamura H., , Dan K., , Yokose N., , Iwakiri R., , Ohta M., , Sakamaki H., , Tohyama K., , Kondo A., , Hyodo H., , Nakamura K., , Yamashita T., , Elisseeva O.A., , Oka Y., , Oji Y., , Sugiyama H., and Ogata K., Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes, Leuk Res 34: ((2010) ), 986-90. |
[8] | Greenberg P., , Cox C., , LeBeau M.M., , Fenaux P., , Morel P., , Sanz G., , Sanz M., , Vallespi T., , Hamblin T., , Oscier D., , Ohyashiki K., , Toyama K., , Aul C., , Mufti G., and Bennett J., International scoring system for evaluating prognosis in myelodysplastic syndromes, Blood 89: ((1997) ), 2079-88. |
[9] | Malcovati L., , Germing U., , Kuendgen A., , Della Porta M.G., , Pascutto C., , Invernizzi R., , Giagounidis A., , Hildebrandt B., , Bernasconi P., , Knipp S., , Strupp C., , Lazzarino M., , Aul C., , and Cazzola M., Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes, J Clin Oncol 25: ((2007) ), 3503-10. |
[10] | Ueda Y., , Mizutani C., , Nannya Y., , Kurokawa M., , Kobayashi S., , Takeuchi J., , Tamura H., , Ogata K., , Dan K., , Shibayama H., , Kanakura Y., , Niimi K., , Sasaki K., , Watanabe M., , Emi N., , Teramura M., , Motoji T., , Kido M., , Usuki K., , Takada S., , Sakura T., , Ito Y., , Ohyashiki K., , Ogawa H., , Suzuki T., , Ozawa K., , Imai K., , Kasai M., , Hata T., , Miyazaki Y., , Morita Y., , Kanamaru A., , Matsuda A., , Tohyama K., , Koga D., , Tamaki H., , Mitani K., , Naoe T., , Sugiyama H., and Takaku F., Clinical evaluation of WT1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes, Leuk Lymphoma 54: ((2013) ), 1450-8. |
[11] | Miyawaki S., , Hatsumi N., , Tamaki T., , Naoe T., , Ozawa K., , Kitamura K., , Karasuno T., , Mitani K., , Kodera Y., , Yamagami T., and Koga D., Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia, Leuk Lymphoma 51: ((2010) ), 1855-61. |
[12] | Greenberg P.L., , Tuechler H., , Schanz J., , Sanz G., , Garcia-Manero G., , Sole F., , Bennett J.M., , Bowen D., , Fenaux P., , Dreyfus F., , Kantarjian H., , Kuendgen A., , Levis A., , Malcovati L., , Cazzola M., , Cermak J., , Fonatsch C., , Le Beau M.M., , Slovak M.L., , Krieger O., , Luebbert M., , Maciejewski J., , Magalhaes Silvia M.M., , Miyazaki Y., , Pfeilstocker M., , Sekeres M., , Sperr W.R., , Stauder R., , Tauro S., , Valent P., , Vallespi T., , Van de Loosdrecht A.A., , Germing U., and Haase D., Revised International Prognostic Scoring System for myelodysplastic syndromes, Blood 120: ((2012) ), 2454-65. |
[13] | Cutler C.S., , Lee S.J., , Greenberg P., , Deeg H.J., , Perez W.S., , Anasetti C., , Bolwell B.J., , Cairo M.S., , Gale R.P., , Klein J.P., , Lazarus H.M., , Liesveld J.L., , McCarthy P.L., , Milone G.A., , Rizzo J.D., , Schultz K.R., , Trigg M.E., , Keating A., , Weisdorf D., , Antin J.H., and Horowitz M.M., A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: Delayed transplantation for low-risk myelodysplasia is associated with improved outcome, Blood 104: ((2004) ), 579-85. |
[14] | de Witte T., , Brand R., , van Biezen A., , Mufti G., , Ruutu T., , Finke J., , von dem Borne P., , Vitek A., , Delforge M., , Alessandrino P., , Harlahakis N., , Russell N., , Martino R., , Verdonck L., , Kroger N., and Niederwieser D., Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: Delay of the transplant is associated with inferior survival, Br J Haematol 146: ((2009) ), 627-36. |
[15] | Ommen H.B., , Nyvold C.G., , Braendstrup K., , Andersen B.L., , Ommen I.B., , Hasle H., , Hokland P., and Ostergaard M., Relapse prediction in acute myeloid leukemia patients in complete remission using WT1 as a molecular marker: Development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals, Br J Haematol 141: ((2008) ), 782-91. |
[16] | JSHCT, The Japan Society for Hematopoietic Cell Transplantation monograph, 19: ((2009) ), 8. |