Acute myeloid leukemia (AML) carrying NPM1 mutations and cyto-plasmic nucleophosmin(NPMc+ AML) accounts for about one-third of adult AML and shows distinct features, including a unique gene expression profile. MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nucleotides in length that have been linked to the development of cancer. Here, we investigated the role of miRNAs in the biology of NPMc+ AML. The miRNA expression was evaluated in 85 adult de novo, AML patients characterized for subcellular localization/mutation status of NPM1 and FLT3 mutations using a custom microarray platform. Data were analyzed by using univariate t test within BRB tools. We identified a strong miRNA signature that distinguishes NPMc+ mutated (n = 55) from the cytoplasmic-negative (NPM1 unmutated) cases (n = 30) and includes the up-regulation of miR-10a, miR-10b, several let-7 and miR-29 family members. Many of the down-regulated miRNAs including miR-204 and miR-128a are predicted to target several HOX genes. Indeed, we confirmed that miR-204 targets HOXA10 and MEIS1, suggesting that the HOX upregulation observed in NPMc+ AML maybe due in part by loss of HOX regulators-miRNAs. FLT3-ITD+ samples were characterized by upregulation of miR-155. Further experiments demonstrated that the up-regulation of miR-155 was independent from FLT3 signaling. Our results identify a unique miRNA signature associated with NPMc+ AML and provide evidence that support a role for miRNAs in the regulation of HOX genes in this leukemia subtype. Moreover, we found that miR-155 was strongly but independently associated with FLT3-ITD mutations.

Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin / R., Garzon; M., Garofalo; M. P., Martelli; R., Briesewitz; L. S., Wang; C., Fernandez Cymering; S., Volinia; C. G., Liu; S., Schnittger; T., Haferlach; A., Liso; D., Diverio; M., Mancini; Meloni, Giovanna; Foa, Roberto; M. F., Martelli; C., Mecucci; C. M., Croce; B., Falini. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 105:10(2008), pp. 3945-3950. [10.1073/pnas.0800135105]

Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin

MELONI, Giovanna;FOA, Roberto;
2008

Abstract

Acute myeloid leukemia (AML) carrying NPM1 mutations and cyto-plasmic nucleophosmin(NPMc+ AML) accounts for about one-third of adult AML and shows distinct features, including a unique gene expression profile. MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nucleotides in length that have been linked to the development of cancer. Here, we investigated the role of miRNAs in the biology of NPMc+ AML. The miRNA expression was evaluated in 85 adult de novo, AML patients characterized for subcellular localization/mutation status of NPM1 and FLT3 mutations using a custom microarray platform. Data were analyzed by using univariate t test within BRB tools. We identified a strong miRNA signature that distinguishes NPMc+ mutated (n = 55) from the cytoplasmic-negative (NPM1 unmutated) cases (n = 30) and includes the up-regulation of miR-10a, miR-10b, several let-7 and miR-29 family members. Many of the down-regulated miRNAs including miR-204 and miR-128a are predicted to target several HOX genes. Indeed, we confirmed that miR-204 targets HOXA10 and MEIS1, suggesting that the HOX upregulation observed in NPMc+ AML maybe due in part by loss of HOX regulators-miRNAs. FLT3-ITD+ samples were characterized by upregulation of miR-155. Further experiments demonstrated that the up-regulation of miR-155 was independent from FLT3 signaling. Our results identify a unique miRNA signature associated with NPMc+ AML and provide evidence that support a role for miRNAs in the regulation of HOX genes in this leukemia subtype. Moreover, we found that miR-155 was strongly but independently associated with FLT3-ITD mutations.
2008
flt3-itd; hox; npm1
01 Pubblicazione su rivista::01a Articolo in rivista
Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin / R., Garzon; M., Garofalo; M. P., Martelli; R., Briesewitz; L. S., Wang; C., Fernandez Cymering; S., Volinia; C. G., Liu; S., Schnittger; T., Haferlach; A., Liso; D., Diverio; M., Mancini; Meloni, Giovanna; Foa, Roberto; M. F., Martelli; C., Mecucci; C. M., Croce; B., Falini. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 105:10(2008), pp. 3945-3950. [10.1073/pnas.0800135105]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/229919
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 206
  • Scopus 435
  • ???jsp.display-item.citation.isi??? 394
social impact