Medico

Leukemia Research 35 (2011) 163–168

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Leukemia Research
journal homepage: www.elsevier.com/locate/leukres

Immunophenotype of acute myeloid leukemia with NPM mutations: Prognostic impact of the leukemic compartment size
J. Nomdedeu a,∗ , E. Bussaglia a , N. Villamor b , C. Martinez a , J. Esteve b , M. Tormo c , C. Estivill a , M.P. Queipo d , R.Guardia e , M. Carricondo a , M. Hoyos a , A. Llorente f , J. Juncà g , M. Gallart h , A. Domingo i , J. Bargay j , M. Mascaró j , J.M. Moraleda k , L. Florensa l , J.M. Ribera g , D. Gallardo e , S. Brunet a , A. Aventin a , J. Sierra a , on behalf of the Spanish CETLAM
a

Department of Hematology and Laboratory, Hospital de la Santa Creu I Sant Pau, Avda. Sant Antoni M. Claret, 167, 08025Barcelona, Spain Department of Hematology, Hospital Clinic, Barcelona, Spain c Department of Hematology, Hospital Clinic, Valencia, Spain d Department of Hematology, Hospital Virgen de la Victoria, Málaga, Spain e Department of Hematology, ICO Girona, Spain f Department of Hematology, Hospital Joan XXIII, Tarragona, Spain g Department of Hematology, Hospital Germans Trias I Pujol, Badalona, Spain hDepartment of Hematology, Hospital Arnau de Vilanova, Lleida, Spain i Department of Hematology, Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain j Department of Hematology, Hospital de Son Llatzer, Palma de Mallorca, Spain k Department of Hematology, Hospital Virgen de la Arrixaca, Murcia, Spain l Department of Hematology, Hospital del Mar, Barcelona, Spain
b

a r t i c l e

i n f oa b s t r a c t
NPM mutations are the most common genetic abnormalities found in non-promyelocytic AML. NPMpositive patients usually show a normal karyotype, a peculiar morphologic appearance with frequent monocytic traits and good prognosis in the absence of an associated FLT3 mutation. This report describes the immunophenotypic and genetic characteristics of a consecutive series of NPM-mutatedde novo AML patients enroled in the CETLAM trial. Eighty-three patients were included in the study. Complete immunophenotype was obtained using multiparametric flow cytometry. Associated genetic lesions (FLT3, MLL, CEBPA and WT1 mutations) were studied by standardized methods. Real-time PCR was employed to assess the minimal residual status. The most common pattern was CD34-CD15+ and HLA-DR+. SmallCD34 populations with immunophenotypic aberrations (CD15 and CD19 coexpression, abnormal SSC) were detected even in CD34 negative samples. Nearly all cases expressed CD33 (strong positivity), CD13 and CD117, and all were CD123+ .The stem cell marker CD110 was also positive in most cases. Biologic parameters such as a high percentage of intermediate CD45+ (blast gate) (>75% nucleated cells),CD123+ and FLT3-ITD mutations were associated with a poor outcome. Quantitative PCR positivity had no prognostic impact either after induction or at the end of chemotherapy. Only PCR positivity (greater than 10 copies) detected in patients in haematological remission was associated with an increased relapse rate. Further studies are required to determine whether the degree of leukemic stem cellexpansion (CD45 + CD123 + cells) increases the risk of acquisition of FLT3-ITD and/or provides selective advantages. © 2010 Elsevier Ltd. All rights reserved.

Article history: Received 1 April 2010 Received in revised form 12 May 2010 Accepted 17 May 2010 Available online 9 June 2010 Keywords: Acute leukemias NPM mutations Flow cytometry Immunophenotype

1. Introduction Acute myeloid leukaemia (AML)is a complex genetic disorder which arises in hematopoietic progenitors. Knowledge of underlying cytogenetic and molecular lesions has provided insight into the

∗ Corresponding author. Tel.: +34 932919000; fax: +34 932919192. E-mail address: jnomdedeu@santpau.cat (J. Nomdedeu). 0145-2126/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2010.05.015...