The findings were presented by Dr Bruno Galy (German Cancer Research Centre, Germany) during the Presidential Symposium [1]. Using a conditional gene knock-out (KO) mouse model to disrupt IRPs, the research team reported that acute loss of IRPs resulted in microcytic anaemia and bone marrow aplasia, which was associated with a corresponding decrease of myeloid cell and erythrocyte counts in peripheral blood. Increased counts of stem and multipotent progenitor cells led to an enlargement of the stem cell compartment. Surprisingly, while common progenitors were amplified in the KO compared with the control mice, increased numbers of differentiated cells were not observed.
The research team concluded that IRPs are important for normal haematopoiesis and differentiation. Notably, neutrophil counts, but not monocyte counts, were substantially decreased in the KO compared with the control mice.
Reciprocal bone marrow transplantation experiments supported a specific role for IRPs in neutrophil differentiation. While wildtype cells could differentiate normally when transplanted into KO mice, KO cells failed to differentiate normally when transplanted into wildtype mice. Transcriptome profiling of neutrophils at different stages of differentiation revealed that the immature neutrophils of KO cells had many differentially expressed genes related to cellular metabolism relative to wildtype neutrophils.
“IRPs seem dispensable for the expansion of haematopoietic stem and progenitor cells,” Dr Galy concluded. “Our main finding is that IRP function is not only important for erythrocyte differentiation but also for neutrophil differentiation.”
- Bonadonna M, et al. A novel role for iron regulatory proteins in hematopoiesis. EHA25 Virtual, 11-21 June 2020, Abstract S104.
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Table of Contents: EHA 2020
Featured articles
Myeloid
VIALE-A: newly diagnosed chemo-ineligible AML
DEC10-VEN superior to intensive chemotherapy in high-risk AML
Magrolimab plus azacitidine: good ORR in MDS/AML
Asciminib monotherapy in Ph+ CML: major molecular responses
CML TKI interruption: Swedish registry results
Patients with lower-risk MDS benefit from imetelstat
Better outcomes adding enasidenib to azacitidine in mIDH2-AML
Lymphoid
PET-stratification can omit radiotherapy in early-stage unfavourable Hodgkin lymphoma
Pembrolizumab improves PFS for relapsed/refractory Hodgkin lymphoma
Promising first-in-human trial of epcoritamab in B-NHL
Two trials: acalabrutinib in CLL
Zanubrutinib versus ibrutinib in Waldenström macroglobulinaemia
Deep responses in R/R CLL with venetoclax monotherapy
MRD assessment post-CAR-T predicts ALL allo-HSCT bridging
Plasma Cell Dyscrasias
Daratumumab for light-chain amyloidosis
Isatuximab triplet improves PFS in R/R MM
Initial results from CAR-T cell therapy in MM: KarMMa
Graft-Versus-Host Disease
GRAVITAS-301: improved complete aGVDH response
Ruxolitinib improves steroid-refractory aGVHD across subtypes
Benign Haematology
Paroxysmal nocturnal haemoglobinuria treatment with pegcetacoplan
Mitapivat, a pyruvate kinase-R activator, in SCD is safe with early efficacy results
SCD LentiGlobin gene therapy: new data on VOC and ACS
Paediatric Haematology
Venetoclax + navitoclax promising for R/R ALL or LL
Nivolumab/brentuximab vedotin in R/R HL: good CMR rates
Bench-to-Bedside Science from the Presidential Symposium
Microbiome predicts B-ALL predisposition
Netrin-1 regulates haematopoietic stem cells
Unrecognised role of iron in neutrophil differentiation
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