molecular monitoring of treatment

Molecular Monitoring of WT1 Gene Expression Degree in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation

BONE MARROW TRANSPLANTATION , , , , ,

N.N. Mamaev, A.V. Gorbunova, I.M. Barkhatov, Ya.V. Gudozhnikova, T.L. Gindina, V.A. Katerina, E.V. Volchkov, A.L. Alyanskii, E.V. Babenko, O.A. Slesarchuk, N.V. Stancheva, S.N. Bondarenko, B.V. Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gorbunova AV, Barkhatov IM, et al. Molecular Monitoring of WT1 Gene Expression Level in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2015;8(3):309–20 (In Russ).

ABSTRACT

Objective. To evaluate the possibility of serial analysis of WT1 gene expression level for prediction and diagnosis of post-transplant acute myeloid leukemia (AML) relapses.

Methods. Serial analyses of WT1 gene expression were performed using quantitative real-time PCR during the post-transplant period of 34 patients with AML. All patients underwent allogeneic hematopoietic stem cell transplantation: unrelated (n = 22), related (n = 12), including haploidentical (n = 4). 5 of 34 patients had AML transformed from the myelodysplastic syndromes (MDS). In addition, the level of donor chimerism and the bone marrow/peripheral blood blast cells counts were evaluated. AML1/ETO (n = 4) or EVI1 (n = 4) gene expression degrees were measured in 8 patients in order to compare those with the WT1 gene expression.

Results. Based on obtained data on the WT1 gene expression, two equal subgroups of patients were formed. The first one consisted of patients with stable normal expression of the investigated molecular indicator during the post-transplant period, whereas the second group consisted of patients with impaired expression. The initial level of WT1 gene expression almost did not depend on both cytological and cytogenetic AML subtypes. During the post-transplant period, the WT1 gene expression degree correlated with that of AML1/ETO or EVI1. Increased WT1 gene expression take the lead over the decreased donor chimerism and blast cell count increase in bone marrow and blood typical for post-transplant relapses of AML.

Conclusion. The higher level of WT1 gene expression may serve not only as a marker for timely diagnosis of post-transplant relapses in AML patients, but also as a monitoring parameter for testing their treatment quality.

Keywords: acute myeloid leukemias, hematopoietic stem cell transplantation, WT1 gene expression monitoring, AML1/ETO and EVI1, diagnosis of post-transplant relapses, molecular monitoring of treatment.

Received: March 19, 2015

Accepted: June 1, 2015

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