Blood Podcast: Season 1, Episode 28
This week we will review data that suggests the pro-inflammatory environment associated with aging alters hematopoietic stem cell function by inducing IL27Ra expression, examine a study attempting to optimize antiplatelet therapy in essential thrombocythemia, and learn more about a study by investigators who have proposed that myelodysplastic syndrome patients with mutations in SF3B1 identify a new subtype of that disease.
SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS
The World Health Organization’s classification of hematopoietic and lymphoid tumors has worked to integrate morphology and genetics, but del(5q) remains the only molecularly defined subtype of myelodysplasia (MDS). In a Special Report that is also this issue’s Plenary Paper, the International Working Group for the Prognosis of MDS makes the case for designating SF3B1-mutant MDS as a second molecularly defined subtype with good prognosis and increased likelihood of response to luspatercept.
A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia
Treatment with once-daily aspirin (acetylsalicylic acid [ASA]) is recommended in essential thrombocythemia (ET) based on efficacy studies in polycythemia vera, but ASA may not provide sufficient platelet inhibition in ET because of increased platelet activation. Rocca et al compared efficacy of ASA in suppressing thromboxane excretion with once-, twice-, and 3-times–daily dosing. Twice-daily dosing has superior antiplatelet activity compared to once-daily dosing, with no further improvement with treatment 3 times daily.
Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties
Garnier and colleagues studied erythrocyte-derived microparticles (MPs) isolated from the plasma of patients with sickle cell disease (SCD) before and after hydroxyurea treatment and during vaso-occlusive crisis. They demonstrated that increased phosphatidylserine (PS) expression on SCD MPs increases endothelial ICAM-1 and neutrophil adhesion at baseline, and this was markedly increased during crisis. Furthermore, PS expression was decreased by hydroxyurea, suggesting a novel effect in preventing crisis.
Aging-induced IL27Ra signaling impairs hematopoietic stem cells
Aging-associated changes in hematopoietic stem cells lead to myeloid skewing, anemia of aging, and increased risk of myeloid malignancy. He et al confirmed that these changes are closely linked to increased expression of inflammatory cytokines, demonstrating that an age-associated increase in tumor necrosis factor α leads to increased expression of interleukin 27 receptor α (IL27Ra) and that these IL27Ra+ stem cells have impaired reconstitution capacity and increased myeloid skewing.
Epo receptor signaling in macrophages alters the splenic niche to promote erythroid differentiation
Chen and colleagues present a novel paradigm of the role of erythropoietin (Epo) in stress hematopoiesis. Using a mouse model, they demonstrated that Epo acts to modulate macrophages in the erythropoietic niche to suppress Wnt expression, suppressing Wnt-induced proliferation of early progenitors, and to increase production of prostaglandin E2, inducing erythroid progenitors to differentiate.
