Immunomodulatory drugs downregulate IKZF1 leading to expansion of hematopoietic progenitors with concomitant block of megakaryocytic maturation
EHA Learning Center. Liu A. Oct 1, 2018; 234248
Topic: 4Bc Mobilization, collection and manipulation of hematopoeitic stem cells
Ailing Liu
Ailing Liu
Login now to access Regular content available to all registered users.

Access to EHA Members only content is an EHA membership benefit.
Click here to join EHA or renew your membership here.


Journal Abstract
Discussion Forum (0)
Rate & Comment (0)

Co-Authors: Shirong Li, Vera Donnenberg, Jing Fu, Susanne M. Gollin, Huihui Ma, Caisheng Lu, Donna B. Stolz, Markus Y. Mapara, Sara A. Monaghan, Suzanne Lentzsch

Abstract: The immunomodulatory drugs, lenalidomide and pomalidomide yield high response rates in multiple myeloma patients, but are associated with a high rate of thrombocytopenia and increased risk of secondary hematologic malignancies. Here, we demonstrate that the immunomodulatory drugs induce self-renewal of hematopoietic progenitors and upregulate megakaryocytic colonies by inhibiting apoptosis and increasing proliferation of early megakaryocytic progenitors via down-regulation of IKZF1. In this process, the immunomodulatory drugs degrade IKZF1 and subsequently down-regulate its binding partner, GATA1. This results in the decrease of GATA1 targets such as ZFPM1 and NFE2, leading to expansion of megakaryocytic progenitors with concomitant inhibition of maturation of megakaryocytes. The down-regulation of GATA1 further decreases CCND1 and increases CDKN2A expression. Overexpression of GATA1 abrogated the effects of the immunomodulatory drugs and restored maturation of megakaryocytic progenitors. Our data not only provide the mechanism for the immunomodulatory drugs induced thrombocytopenia but also help to explain the higher risk of secondary malignancies and long-term cytopenia induced by enhanced cell cycling and subsequent exhaustion of the stem cell pool.

Article Number: 1688

Doi: 10.3324/haematol.2018.188227

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings