Anti-malaria benefit of hydroxyurea in SCA, IL-22 in the treatment in lower GI acute GVHD, and FLT3^ITD changes depend on context in AML

In this week’s episode we will review a study in sub-Saharan Africa where treatment of sickle cell anemia with hydroxyurea is associated with a lower incidence of malaria. New research suggests mild myelosuppression associated with hydroxyurea treatment may actually have a salutary effect. Next, a potential new treatment approach in lower GI acute GVHD. Adding an interleukin-22 therapy to corticosteroid treatment was well tolerated with a high rate of response in this very challenging patient population. Finally, common AML driver mutations such as FLT3^ITD (or internal tandem duplications) orchestrate distinct transcriptional and epigenetic programs based on different genetic contexts. In the context of a common pediatric AML mutation, FLT3^ITD selectively activated type I interferon signaling, suggesting a distinct therapeutic vulnerability.

Released March 23, 2023

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The articles highlighted in this episode are listed below:

• Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia (or SCA) in sub-Saharan Africa

  Authors: Peter Olupot-Olupot, George Tomlinson, Thomas N. Williams, Léon Tshilolo, Brígida Santos, Luke R. Smart, Kathryn McElhinney, Thad A. Howard, Banu Aygun, Susan E. Stuber, Adam Lane, Teresa S. Latham, Russell E. Ware for the REACH Investigators

• HU for SCA in Africa: associated malaria benefit

  Author: Isaac Odame

• A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract

  Authors: Doris M. Ponce, Amin M. Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet S. Sandhu, Juliet N. Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel-Angel Perales, Gillian Moore, Samira Fatmi, Cristina Soto, Antonio Gomes, Paul Giardina, LeeAnn Marcello, Xiaoqiang Yan, Tom Tang, Kevin Dreyer, Jianmin Chen, William L. Daley, Jonathan U. Peled, Marcel R. M. van den Brink, Alan M. Hanash

• IL-22, a new beacon in gastrointestinal aGVHD

  Authors: Mohamad Mohty, Florent Malard

• FLT3^ITD drives context-specific changes in cell identity and variable interferon dependence during AML initiation

  Authors: Yanan Li, Wei Yang, Riddhi M. Patel, Emily B. Casey, Elisabeth Denby, Jonny Mendoza-Castrejon, Priscilla Rodriguez-Lopez, Jeffrey A. Magee

• Context is key for FLT3-ITD

  Author: Sara E. Meyer