Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AM...

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. Mutations in fms-like tyrosine kinase 3 (FLT3) gene including internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain (TKD) as well as in nucleoplasmin (NPM1) gene are associated with pathogenesis of acute myeloblastic leukemia (AML)....

OBJECTIVE Mutations of the nucleophosmin (NPM1) gene are considered as the most frequent acute myeloid leukemia (AML)-associated genetic lesion, reported with various incidences in different studies, and type A (NPM1-A) is the most frequent type. However, since most series in the literature report on the features of all patients regardless of the type of mutation, NPM1-A(+) cases have not been ...

OBJECTIVE Somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, are the most frequent mutations in patients with acute myeloid leukemia. The aim of the study was to assess the prevalence and prognostic impact of NPM1 gene mutations in adult AML patients. MATERIALS AND METHODS Polymerase chain reaction and single-strand conformation polymo...

NPM1 belongs to a new category of genes that function both as oncogenes and tumor suppressor genes, depending on gene dosage, expression levels, interacting partners, and compartmentalization. Nucleophosmin mutations within exon 12 have been described as the most frequent acquired molecular abnormalities in adult and pediatric acute myeloid leukaemia (AML), mutation can be observed in nearly ha...

PURPOSE To determine the clinical relevance of mutations in the CCAAT/enhancer binding protein alpha (CEBPA) gene in acute myeloid leukemia (AML) and to examine factors that might modify prognostic impact. PATIENTS AND METHODS The entire CEBPA coding sequence was screened in 1,427 young adult patients with AML, excluding acute promyelocytic leukemia, using denaturing high-performance liquid c...

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Two well defined mutations, including the NPM1 and CCAAT/enhancer-binding protein-alpha (CEBPA) genes, are generally accepted as a better prognosis in AML [1]. NPM1, one of frequent mutations in AML, have been described in association with several clinical f...

NPM1 is the most frequently mutated gene in AML and the role of the NPM1 mutant in acute myeloid leukemia along with its leukemogenic potential are still under investigation.NPM1 genetic alterations can contribute to leukemogenesis through the direct oncogenic effect of the mutant protein and the concomitant loss of one functional allele. Npm1 loss determines tumor development in the mouse whil...

ence is sufficient to disrupt the nucleolar structure.9 Similarly, the anticancer peptide CIGB-300 leads to nucleolar disassembly and apoptosis, most likely through its capability to bind NPM1.10 Because AML cells carrying the NPM1 mutation are depleted of wild-type NPM1 protein in their nucleolar pool (because of haploinsufficiency and cytoplasmic dislocation through formation of heterodimers ...

BACKGROUND Previous studies have suggested that NPM1 mutations may be a marker for response to all-trans retinoic acid (ATRA) given as an adjunct to intensive chemotherapy in older patients with acute myeloid leukemia (AML). PATIENTS AND METHODS We examined the impact of the addition of ATRA among patients with diploid cytogenetics treated on a randomized phase II study of fludarabine + cytar...