Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC

Abstract

Articles and Brief Reportshaematologica | 2012; 97(2) 241 IntroductionThe overall prognosis for adult acute myeloid leukemia (AML) remains poor. Cytogenetic analysis provides the major prognostic information, 1 but more than 40% of patients have normal cytogenetics (CN-AML). In these cases, many molecular alterations with prognostic significance have been described to guide treatment. Mutations involving nucleophosmin (NPM1) and the CCAAT/enhancer binding protein alpha (CEBPA) have been included as references in the World Health Organization classification of AML, and examination for mutations of FLT3 is also strongly recommended. 2 Moreover, many other molecular alterations and/or deregulation of gene expression have been identified and analyzed, such as brain and acute leukemia cytoplasmic protein (BAALC) expression. [3][4][5] Unfortunately, their prognostic value has not been shown in all studies. 6 In addition to these markers, the prognostic role of ABC proteins has been well characterized.7 Among them, the best known is ABCB1 (MDR1/Pgp) whose expression and activity 8 have been associated with poor outcome. However, the role of other members of the ABC protein family has also been described. 9,17 To our knowledge, relationships between ABC proteins and those molecular markers have not yet been explored, except for FLT3/ITD. 10 Whether ABC protein activity at the time of diagnosis remains an independent prognosis factor in adult AML, despite the use of these new molecular markers, should be evaluated.Here we explore the relationships between ABC protein activity, FLT3/ITD, NPM1, CEBPA, and BAALC expression, and evaluate whether ABC protein activity remains a prognostic factor and can be helpful for therapeutic decisions in 111 CN-AML patients who underwent the same treatment according to EORTC protocols. Design and Methods Patients and treatmentsBone marrow or blood samples from the time of diagnosis were Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC September 23, 2011. Manuscript accepted on September 26, 2011 ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyrosine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAATenhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATPbinding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survi...

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