New insights into the biology of acute myeloid leukemia with mutated NPM1

  • Lorenzo Brunetti
  • Michael C. Gundry
  • Margaret A. GoodellEmail author
Progress in Hematology Epigenetic abnormalities and therapies for hematological malignancies


Acute myeloid leukemia (AML), the most common acute leukemia in adults, increases exponentially with age. While a number of recent advances have improved treatment, high cure rates have not yet been achieved. Nucleophosmin (NPM1) is found mutated in nearly one-third of newly diagnosed cases and leads to NPM1 protein that is mislocalized to the cytoplasm instead of the nucleolus. If the mechanistic basis through which this mislocalization leads to malignancy could be revealed, this AML subtype may be targetable with new drugs. Here, we review the structure and functions of the normal and mutant forms of nucleophosmin. We discuss several recent studies that have shed light on the pathophysiology of NPM1 mutations. We discuss the importance of HOX gene misregulation in NPM1-mutated leukemias, as well as evidence for the reliance of mutated NPM1 on its continued nuclear export. Together, these aspects, as well as new tools to manipulate and study NPM1, open the door to new therapeutic strategies that may ultimately improve treatment of this common subtype of AML.


NPM1 B23 HOX Acute myeloid leukemia AML XPO1 



This work has been supported by the NIH (DK092883, CA183252) and the Samuel Waxman Cancer Research Foundation.


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© Japanese Society of Hematology 2019

Authors and Affiliations

  1. 1.The Stem Cells and Regenerative Medicine CenterBaylor College of MedicineHoustonUSA
  2. 2.Center for Cell and Gene Therapy, Texas Children’s Hospital, Houston Methodist HospitalBaylor College of MedicineHoustonUSA
  3. 3.Centro Ricerca Emato-Oncologica (CREO)Università degli Studi di PerugiaPerugiaItaly
  4. 4.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  5. 5.Department of PediatricsBaylor College of MedicineHoustonUSA

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