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Title of Journal: Ann Hematol

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Abbravation: Annals of Hematology

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Springer Berlin Heidelberg

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DOI

10.1007/978-3-319-18687-0_6

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1432-0584

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Emphasis Type="Italic"FLT3/EmphasisITD and E

Authors: Barbara NasilowskaAdamska Iwona Solarska Monika Paluszewska Iwona Malinowska Wieslaw W Jedrzejczak Krzysztof Warzocha
Publish Date: 2013/09/13
Volume: 93, Issue: 4, Pages: 577-593
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Abstract

Fmslike tyrosine kinase 3–internal tandem duplication FLT3ITD and mixedlineage leukemia gene–partial tandem duplication MLLPTD are aberrations associated with leukemia which indicate unsatisfactory prognosis Downstream regulatory targets of FLT3ITD and MLLPTD are not well defined We have analyzed the expression of MDR1 multidrug resistant protein1 MRP1 breast cancer resistance protein BCRP and lung resistance protein LRP messenger RNA mRNA in relation to the mutational status of FLT3ITD and MLLPTD in 185 acute myeloid leukemia AML adult patients The realtime quantitative polymerase chain reaction method was performed to assess the expression of the MDR1 MRP1 BCRP and LRP mRNA and the results were presented as coefficients calculated using an intermediate method according to Pfaffl’s rule Significantly higher expressions of MDR1 mRNA were found in patients who did not harbor FLT3ITD 020 vs 005 p = 00001 and MRP1 mRNA in patients with this mutation 096 vs 070 p = 0002 and of BCRP mRNA in patients with MLLPTD 061 vs 038 p = 003 In univariate analysis the high expression of MDR1 mRNA ≥01317 negatively influenced the outcome of induction therapy p = 005 whereas the high expression of BCRP mRNA ≥11487 was associated with a high relapse rate RR p = 0013 We found that the high expression of MDR1 ≥01317 MRP1 ≥08409 and BCRP mRNA ≥11487 significantly influenced diseasefree survival DFS p = 0059 0032 and 0009 respectively and overall survival 0048 0014 and 0059 respectively Moreover a high expression of BCRP mRNA ≥11487 proved to be an independent prognostic factor for RR p = 001 and DFS p = 0002 in multivariate analysis The significant correlation between the expression of MDR1 MRP1 and BCRP mRNA and FLT3ITD or MLLPTD in AML patients requires further investigationThe authors thank Prof Barbara PienkowskaGrela and Dr Katarzyna Borg for the cytogenetic analysis and Dr Jolanta Wozniak and Dr Urszula Podstawka for immunophenotyping in AML patients and their contribution to this study Moreover the authors thank Richard Szydlo for the support in the statistical analyses performed in this study This project was supported by a grant from The Polish Ministry of Science no N402 208935

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