Issue Archive

Cholesterol is a multifaceted molecule that regulates cell permeability and integrity and inflammatory responses. Brendolan and Russo review the role of cholesterol homeostasis in hematological malignancies, as well as in cells of the tumor microenvironment, and discuss the potential use of lipid modulators for therapeutic purposes based on existing preclinical data.

Langerbeins and colleagues report the first randomized study of early intervention with a novel targeted agent in patients with asymptomatic chronic lymphocytic leukemia (CLL). The data indicate that treatment of patients with early-stage CLL bearing unfavorable prognostic factors, but not yet meeting standard criteria for initiation of therapy, are less likely to experience symptomatic progression if commenced on ibrutinib than a placebo. Further follow-up is required to determine whether these data have any implication for routine practice.

Transcriptomic studies of hematopoietic stem cells (HSCs) have revealed increased expression of the gene encoding syndecan-2, a heparan sulfate proteoglycan. Using classical cell sorting, functional and transplant studies, Termini and colleagues identified syndecan-2 as a useful cell surface marker to enrich long-term repopulating murine HSCs, and they demonstrate its importance in regulating HSC self-renewal via control of stem cell quiescence.

CXCR is overexpressed in mucosa-associated lymphoid tissue (MALT) lymphoma. Mayerhoefer et al report the prospective assessment of a CXCR4-targeting positron emission tomography (PET) tracer for the noninvasive response assessment of gastric MALT lymphoma. By prospectively analysing⁶⁸ Ga-pentixafor PET images and using time-matched gastric biopsies, they demonstrate that this imaging modality accurately identifies residual gastric MALT lymphoma after Helicobacter pylori eradication with a sensitivity of 95%.

Understanding the biology of histiocytic neoplasms has enabled the rational application of targeted therapies for these rare diseases. Kemps and colleagues report clinicopathologic, molecular, treatment, and follow-up data in a large cohort of patients with a recently recognized disease entity, ALK-positive histiocytosis. The disease is tightly associated with KIF5B-ALK fusions, and ALK inhibition induces robust and durable responses.

Subburaj et al report metabolomic analyses of samples from 222 pediatric and adolescent allogeneic transplant patients followed longitudinally as part of the prospective ABLE (Applied Biomarker of Late Effects of Childhood Cancer) biomarker trial. In multiregression analysis, plasma α-ketoglutaric acid is consistently elevated both before and at the onset of chronic graft-versus-host disease (GVHD), suggesting that metabolomic profiling can distinguish late acute GVHD from chronic GVHD.