Issue Archive

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.

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.

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.

Myeloid-derived suppressor cells (MDSCs) are a subset of mature neutrophils that promote tumor growth through suppression of T-cell responses. Perez et al characterize MDSCs in multiple myeloma, proposing a combination of markers to identify this subpopulation and correlating their frequency with inferior progression free survival.

Stromal adhesion mediated by integrin α6 has been implicated in both drug resistance and central nervous system migration of B-cell acute lymphoblastic leukemia (B-ALL) cells. The authors demonstrated that blocking α6 induces apoptosis in B-ALL cells and increases their sensitivity to chemotherapy, suggesting that α6 is a potential novel target for B-ALL therapy.

Acute myeloid leukemia (AML) associated with inv(3)/t(3;3) is recognized as a distinct form of AML associated with poor prognosis. Ottema and colleagues dissected the genotypic and functional characteristics of atypical 3q26/MECOM rearrangements in AML, demonstrating that they have a similar pattern of gene expression to inv(3)/t(3;3) and suggesting that all 3q26-rearranged AML should be viewed as a single entity.

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.

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.