HemaBites showcase hematology news and short commentaries on recent high-impact articles published in international journals. This blog will keep you up to date with the latest developments and discoveries in the field of hematology.

Friday, May 18, 2018

Obituary: Hans Erik Johnsen 1948-2018

Pieter Sonneveld

President European Hematology Association. Erasmus MC Cancer Institute, Rotterdam, the Netherlands

Hans Erik Johnsen 1948-2018.pngOn May 17, 2018, just after his 70th birthday, Hans Erik Johnsen passed away.

Hans Johnsen was Professor of Clinical Hematology at the Department of Hematology at Aalborg University in Denmark. He was trained as a specialist in Internal Medicine and Hematology in Aarhus University, where he also completed his PhD thesis, entitled: "Lymphocyte subpopulations in man. Identification by membrane markers and functional characterization." This interest in lymphoid biology and neoplasms would guide his scientific development and career.

For several years Hans was a member of the EHA Scientific Program Committee responsible for composing EHA's Congress Program; a role he fulfilled with dedication and flair. In addition, he chaired and presented in numerous sessions always pursuing the importance of hematology research, especially in the field of Multiple Myeloma; an area in which he was a great expert..

Hans also has had major contributions to the European Myeloma Network. He was a founding member, board member and secretary of "European Myeloma Network" (EMN) from 2004. In 2007, he became the coordinator of the European Myeloma Stem cell Network (MSCNET), funded by EU FP6.. He was still actively pursuing scientific questions and presented interesting data at the recent Myeloma Workshop in Torino.

​He has coordinated numerous scientific projects and grants, published 286 scientific articles in peer-reviewed journals and supervised more than 50 PhD and Master students

Hans Johnsen was a great scientist and an original investigator. He was also a friendly and pleasant person and colleague. It was an honour and pleasure to work with him. His contributions to the founding and development of the European Myeloma Network have been significant and essential for its current success. Our sympathy goes to his family and friends. 

Friday, April 6, 2018

Acute Myeloid Leukemia (AML) – Hitting the FLT3 Target

Lars Bullinger 

Department of Hematology, Oncology and Tumor Immunology; and Charité-University-Medicine Berlin, Germany

In acute myeloid leukemia (AML), FLT3 tyrosine kinase mutations such as internal tandem duplications (ITD) are often associated with an unfavorable prognosis, and thus many FLT3-ITD patients undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). While outcome of relapse after allo-HSCT is usually dismal, treatment with sorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), has resulted in durable remission in some patients (Metzelder et al. 2017). Mathew and colleagues now provide a stunning molecular rationale for this observation (Mathew et al. 2018). They could demonstrate that kinase inhibitors like sorafenib can increase the production of IL-15 by FLT3-ITD positive AML cells. IL-15 then synergizes with the allogeneic CD8+ T-cell response, thereby leading to long-term survival in FLT3-ITD mouse leukemia models. Mechanistically, sorafenib leads to a reduction in the expression of the transcription factor ATF4, thereby inhibiting the interferon regulatory factor 7 (IRF7) activation block, which in turn enhances IL-15 transcription. Thus, in patients with FLT3-ITD positive AML relapsing after allo-HSCT, multi-targeted TKI treatment might confer an immune-mediated cure. Given the recent approval of the multi-targeted TKI midostaurin for FLT3 mutant AML (Stone et al. 2017), it will be interesting to see whether TKI use not only in case of relapse, but also as maintenance therapy following allo-HSCT will have a positive impact on outcome.


Figure 1: Mathew and colleagues propose that FLT3 inhibition by sorafenib (or other TKIs) leads to increased IL-15 transcription because it takes away downstream FLT3 receptor tyrosine kinase signaling, which normally leads to ATF4 production. Diminished ATF4 levels result in decreased inhibition of IRF7 phosphorylation and activation. This in turn leads to more active phosphorylated IRF7, which can translocate to the nucleus, where it activates IL-15 transcription. The link between oncogenic FLT3 signaling and ATF4-mediated inhibition of IL-15 production could serve as tumor escape mechanism.[Scheme kindly provided by R. Zeiser]


1. Mathew et al. Nat Med. 2018 Mar;24(3):282-291. doi: 10.1038/nm.4484.

2. Metzelder et al. Eur J Cancer. 2017 Nov;86:233-239. doi: 10.1016/j.ejca.2017.09.016.

3. Stone et al. N Engl J Med. 2017 Aug 3;377(5):454-464. doi: 10.1056/NEJMoa1614359.​

Friday, April 6, 2018

Vessel-housekeeping monocytes: towards a novel target in sickle cell disease

Francesca Vinchi, PhD

Lindsley F. Kimball Research Institute (LFKRI), New York Blood Center - NYBC, New York, USA.

Recent insights in the pathomechanisms of painful vaso-occlusive crises (VOC), a hallmark of sickle cell disease (SCD), have unraveled the critical role of hemoglobin-derived heme released during hemolytic events, as an "alarmin" capable of activating the immune system and damaging the vascular endothelium.

In a recent issue of Blood, Yunfeng Liu and colleagues explored the vascular-protective role of a specific subset of endothelial patrolling monocytes (PMos) in SCD.

This monocyte subset is characterized by elevated levels of the heme-degrading enzyme HO-1 (HO-1hi) and reduced expression of inflammatory cytokines in SCD. Using labeling experiments, the authors demonstrated that a direct interaction of monocytes with endothelial cells (ECs) exposed to heme, followed by phagocytosis of heme-injured ECs, is a requisite for HO-1hi PMo generation.

Importantly, the HO-1hi PMo subset was reduced in SCD patients experiencing recent or recurrent VOC events, suggesting that inappropriately low HO-1hi PMos is a predisposing factor to VOC in SCD. The enhanced heme-induced vascular stasis of sickle erythrocytes in a PMo-ablated mouse line highlighted the critical "housekeeping" function of HO-1hi PMos in the removal of hemolysis-injured ECs in the SCD vasculature and in lowering VOC risk.

Future studies will uncover in the near future the potential of PMo manipulation for therapeutic applications in SCD.


Figure 1. Hypothetical anti-VOC function of HO-1hi PMos. Hemolytic events lead to the release of free hemoglobin-derived heme, causing endothelial cell (EC) activation and damage. The authors propose that increased expression of adhesion molecules and phosphatidylserine (PS) on ECs promotes the recruitment of patrolling monocytes (PMos) along the endothelial lining. PMos remove heme-injured ECs and cell debris, switching into a subset of high HO-1 (HO-1hi) expressing monocytes with anti-inflammatory and housekeeping properties. Elevated HO-1hi PMos decrease (a), whereas low HO-1hi PMos increase (b) the risk of VOC in SCD.


Yunfeng Liu et al., HO-1hi patrolling monocytes protect against vaso-occlusion in sickle cell disease. Blood 2018 Feb 2. pii: blood-2017-12-819870. doi: 10.1182/blood-2017-12-819870. 

Tuesday, March 20, 2018

The kinase inhibitor sorafenib boosts graft-versus-leukemia activity

Jan Cools

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against FLT3-ITD positive AML. The authors1 found that that the synergism of T cells and sorafenib was mediated via activation of the IRF7–IL15 axis in leukemia cells, which resulted in metabolic reprogramming of leukemia-reactive T cells. 


1.Mathew NR et al. Nature Medicine, March 2018 https://www.nature.com/articles/nm.4484

Tuesday, March 20, 2018

The mRNA decapping enzyme DCPS as a new target for AML therapy  

Jan Cools

The authors1 performed a genome-wide CRISPR-Cas9 screen in AML cell lines and identified the mRNA decapping enzyme scavenger (DCPS) as an essential gene. Interestingly, DCPS inhibitors already exist and RG3039 showed anti-leukemic activity via inducing pre-mRNA mis-splicing. These findings identify DCPS as a novel target for the treatment of AML.


1. Yamauchi T et al. Cancer Cell, March 2018​ http://www.cell.com/cancer-cell/abstract/S1535-6108(18)30012-6