Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects

Mara Mazzola, Alex Pezzotta, Grazia Fazio, Alessandra Rigamonti, Erica Bresciani, Germano Gaudenzi, Maria Chiara Pelleri, Claudia Saitta, Luca Ferrari, Matteo Parma, Monica Fumagalli, Andrea Biondi, Giovanni Cazzaniga, Anna Marozzi, Anna Pistocchi

Research output: Contribution to journalArticlepeer-review


The transcription factor RUNX1, a pivotal regulator of HSCs and haematopoiesis, is a frequent target of chromosomal translocations, point mutations or altered gene/protein dosage. These modifications lead or contribute to the development of myelodysplasia, leukaemia or platelet disorders. A better understanding of how regulatory elements contribute to fine-tune the RUNX1 expression in haematopoietic tissues could improve our knowledge of the mechanisms responsible for normal haematopoiesis and malignancy insurgence. The cohesin RAD21 was reported to be a regulator of RUNX1 expression in the human myeloid HL60 cell line and during primitive haematopoiesis in zebrafish. In our study, we demonstrate that another cohesin, NIPBL, exerts positive regulation of RUNX1 in three different contexts in which RUNX1 displays important functions: in megakaryocytes derived from healthy donors, in bone marrow samples obtained from adult patients with acute myeloid leukaemia and during zebrafish haematopoiesis. In this model, we demonstrate that alterations in the zebrafish orthologue nipblb reduce runx1 expression with consequent defects in its erythroid and myeloid targets such as gata1a and spi1b in an opposite way to rad21. Thus, also in the absence of RUNX1 translocation or mutations, additional factors such as defects in the expression of NIPBL might induce haematological diseases.

Original languageEnglish
Pages (from-to)6272-6282
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Issue number11
Publication statusPublished - Jun 1 2020


  • AML
  • haematopoiesis
  • RUNX1
  • zebrafish

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


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