Data di Pubblicazione:
2018
Citazione:
NIPBL a new player with NPMc+ in the onset of acute myeloid leukemia / M. Mazzola, G. Fazio, G. De florian, L. Ferrari, M. Spreafico, C. Saitta, L. Ferrari, E. Bresciani, A. Biondi, F. Cotelli, M. Fumagalli, M. Parma, P. Riva, A. Marozzi, G. Cazzaniga, A. Pistocchi. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Milano nel 2018.
Abstract:
Cohesins form a multimeric protein complex (SMC1A, SMC3, RAD21, STAG and additional proteins NIPBL, MAU2, ESCO1, HDAC8) involved in the cohesion of sister chromatids, post-replicative DNA repair and transcriptional regulation. Recently, recurrent somatic mutations and deletions of cohesins have been reported in the 10% of the patients with Acute Myeloid Leukemia (AML) or other myeloid neoplasms. Frequently, mutations in cohesin genes co-occurred with the known AML-associated gene nucleophosmin (NPM1) that, when mutated, aberrantly relocates to the cytoplasm (NPMc+). Forced NPMc+ expression in zebrafish embryos causes an expansion of hematopoietic stem cells (HSCs) according with AML patient features.
In our cohort of adult AML patients, we observed a specific and significative reduction of the NIPBL expression in NPMc+ patients. We generated a zebrafish model of nipblb haploinsufficiency to investigate the hematopoietic phenotype and the interactions between NPMc+ and nipblb. In nipblb-loss-of-function zebrafish embryos, we observed an increase in myeloid progenitors, a phenotype resembling the NPMc+ zebrafish model. Therefore, we characterize the functional interaction between NPMc+ and NIPBL in the onset of the aberrant hematopoietic phenotype in zebrafish and showed the involvement of the canonical Wnt pathway in this process.
We demonstrate for the first time a role for NIPBL during zebrafish hematopoiesis and that its decreased expression, due to NPM1 mutations, might play a role in leukemia onset.
Funding grant: My First AIRC grant (MFAG) 18714
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
M. Mazzola, G. Fazio, G. De florian, L. Ferrari, M. Spreafico, C. Saitta, L. Ferrari, E. Bresciani, A. Biondi, F. Cotelli, M. Fumagalli, M. Parma, P. Riva, A. Marozzi, G. Cazzaniga, A. Pistocchi
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