%0 Journal Article
%T Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level
%A Marianna Greco
%A Giovanni Caocci
%A Antonio Ledda
%A Adriana Vacca
%A Marcella Arras
%A Ivana Celeghini
%A Giorgio La Nasa
%J Case Reports in Hematology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/896394
%X Despite major advances in the treatment of acute promyelocytic leukemia (APL), the problem of early death (ED) remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD), hypogranular variant morphology, and the bcr-3 isoform of PML-RAR¦Á. We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1). Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL. 1. Introduction Early death (ED) in acute promyelocytic leukemia (APL) occurs in approximately 10 to 25 percent of patients within 30 days of starting induction chemotherapy and is frequently associated with severe hemorrhagic complications [1]. Although the addition of all-trans-retinoic acid (ATRA) to treatment regimens has considerably improved complete remission (CR) rates, the incidence of ED continues to be around 20% [2]. Elevated absolute blast and promyelocyte counts, high prothrombin time at presentation, thrombocytopenia, older age, and anemia have been reported as risk factors associated with ED in APL patients [3]. The aim of this report is to further clarify the clinical significance of molecular genetic parameters in the pathogenesis of hemorrhagic complications and ED in APL. The PML-RAR¦Á transcript subtypes referred to as long (L or bcr-1), variant (V or bcr-2), and short (S or bcr-3), depending on the location of breakpoints within the PML site (intron 6, exon 6, and intron 3), have not been clearly associated with different prognosis or ED in APL [4]. Internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) portend poor prognosis in acute leukemias and have recently been found capable of predicting ED in pediatric patients with acute APL [5]. Despite several reports of association between FLT3-ITD and other characteristics of APL, including elevated white blood cell (WBC) counts, hypogranular variant morphology (M3v), and the short (bcr-3) isoform of PML-RAR¦Á, the prognostic significance of FLT3 mutations still needs to be firmly established [6]. Wilms¡¯ tumor gene 1 (WT1), located on the short arm of chromosome 11, is expressed in most patients with acute myeloid leukemia (AML) or lymphocytic leukemia (ALL) [7]. APL represents the AML subtype with the highest WT1 expression levels. A recent study found that high WT1 mRNA
%U http://www.hindawi.com/journals/crihem/2013/896394/