IDENTIFICATION OF DRIVER AND SUBCLONAL MUTATIONS IN MYELOFIBROSIS AND ACUTE MYELOID LEUKEMIA POST CLASSIC MYELOPROLIFERATIVE NEOPLASMS (MPN)

KAREN SCHEPS; ALICIA ENRICO; CARLOS DE BRASI; CAROLINA MEYER; PAULA HELLER; IRENE LARRIPA; LEANDRO GUTIERREZ; MARIANA RODRÍGUEZ ZUBIETA

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Introduction: Classic MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Evolution to secondary myelofibrosis is part of the natural history of the first two syndromes and, at any stage, acute myeloid leukemia (AML) can be acquired.MPNs are characterized by the presence of driver oncogenic mutations in JAK2, CALR and MPL genes, being mutually exclusive. Also secondary subclonal mutations have been reported in ASXL1, IDH1, IDH2 genes, among others, associated with disease progression.Aims: Analyze the presence of drivers and subclonal mutations in patients with MF and AML post MNP and determine its prognostic impact.Patients and Methods: DNA of 35 patients with MF or AML post MPN were analyzed. JAK2V617F mutation was studied by DARMs PCR. The Allele burden of this mutation was assessed by qPCR. Type 1 and 2 CALR mutations (exon 9) were investigated by PCR and electrophoresis. MPL (exon 10) and ASXL1 (exon 13) mutations were analyzed by PCR and direct sequencing. The mutations IDH1/2 were screened by CSGE.Results: Mutations JAK2V617F, CALR and MPL were detected in 24 (68.5%), 3 (8.5%) and 2 (5.7%) cases respectively, 4 (11.4%) were triple negative and in 2 cases the studies remain incomplete. The mean of the allele burden of the JAK2V617F mutation was 62.7%, splitting the patients into 2 groups with high and low levels. The analysis of exon 13 of ASXL1 revealed 4 indels (3 not previously reported) and 3 rare missense variants. Five of these patients had disease progression or AML evolution. No mutations in the IDH1/2 genes have been detected yet.Discussion: Distribution of driver mutations differs from the literature, with a higher prevalence of JAK2V617F at expense of CALR. The highest allele burden was detected in patients with secondary MF post PV. ASXL1 indel mutations allowed identifying patients at increased risk, reinforcing the importance of these studies to choose the best risk-adapted therapy.