CD34+ cells from AML with mutated NPM1 harbor cytoplasmic mutated nucleophosmin and generate leukemia in immunocompromised mice

Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases

“…NPMc þ AMLs are frequently CD34 negative (Taussig et al, 2010) and they often show multi-lineage involvement (Pasqualucci et al, 2006). However, it has been recently shown that the rare CD34 þ blasts purified from these patients can engraft in immunocompromised mice and support the development of a leukemia that recapitulates the original patient's disease (Martelli et al, 2010). NPM1 mutations arise, in most cases, in primary AML, they are not present in other tumor types (Falini et al, 2005), and they have rarely been found in myeloproliferative or myelodysplastic disorders (Caudill et al, 2006;Oki et al, 2006;Zhang et al, 2007) or in secondary AML.…”

High levels of CD34+CD38low/-CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia: a Groupe Ouest-Est des Leucemies Aigues et Maladies du Sang (GOELAMS) study

“…8,9 Taussig et al revealed a bias in experimental conditions and demonstrated that the leukemic stem cell phenotype was more heterogeneous than previously thought. 10 Moreover it was recently demonstrated that although all immature AML subpopulations may contain leukemic stem cells in a different model of human AML cell transplantation in NOD/SCID/IL2rγ null mice, [11][12][13] 14 More importantly and regardless of their 'stemness' properties, it has been demonstrated both in vitro and in vivo that CD34 + CD38 low/-cells are significantly more resistant than the leukemic bulk population to classical chemotherapeutic agents. 13,15 Previous studies have emphasized the correlation between the enrichment of the CD34 + or CD34 + CD38…”

Downregulation of MEIS1 impairs long-term expansion of CD34+ NPM1-mutated acute myeloid leukemia cells

“…1 Deletion of 5q encompassing the NPM1 locus occurs in B40% of high-risk myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) with complex karyotypes, 2 although the common 5q interstitial deletion that occurs in MDS does not include this region. 3 Mice genetically engineered to harbor heterozygous loss of Npm1 (Npm1 þ /À) were shown to have a mild MDS-like phenotype characterized by dyserythropoiesis and dysplastic megakaryocytes with macrocytic anemia, but without significant cytopenias or alterations in lineage commitment. These mice also exhibited increased susceptibility to hematological malignancies with age.…”

“…Recently, this question has been addressed by two research groups. Taussig et al 2 describe that the CD34 À fraction of NPMc þ AML contains cells that could engraft immunocompromised mice in all studied samples, whereas Martelli et al 3 showed that in most cases the CD34 þ , but not CD34 À cells generated NPMc þ AML in immunocompromised mice.…”