HLA-DQ heterodimers and transplantation, the genomic landscape of LGL leukemia, and an updated classification of hemochromatosis
In this week’s episode we’ll feature new research demonstrating that certain HLA-DQ heterodimers can help predict clinical outcome following hematopoietic cell transplantation. Next, we’ll review a recent integrated and comprehensive genomic analysis that sheds new light on the molecular characteristics of large granular lymphocyte leukemia and its subtypes. Finally, we’ll review the work of a group that proposes a new and more accessible hemochromatosis classification system based on clinical characteristics and genetic features.
HLA-DQ heterodimers in hematopoietic cell transplantation
Relapse after hematopoietic stem cell transplant (HSCT) remains the most common cause of mortality after HSCT. Previously, matching at the class 2 locus, HLA-DQ, has not been considered to be of major relevance to outcomes, but in this Plenary paper, Petersdorf et al demonstrate that specific heterodimers of HLA-DQ α and β chains are associated with higher rates of relapse and decreased disease-free survival. These findings may alter algorithms for HSCT donor selection and stimulate new investigations into the modulation of graft-versus-tumor activity.
Genomic landscape of TCRαβ and TCRγδ T-large granular lymphocyte leukemia
In this month’s CME article, Cheon and colleagues report results of an integrated genomic approach to better define and classify large granular lymphocyte leukemia (LGLL) subtypes. By overlaying the STAT3 mutation status, the authors defined distinct molecular signatures, revealed the common co-occurrence of epigenetic regulator gene alterations, and identified STAT3 mutation-specific clinical associations for this uncommon neoplasm. These data help us better understand the clinical heterogeneity of LGLL.
Critical role of Lama4 for hematopoiesis regeneration and acute myeloid leukemia progression
The hematopoietic niche is disordered and plays a functional role in stress hematopoiesis and acute myeloid leukemia (AML). Cai and colleagues used murine models and human in vitro studies to show that Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is required for normal recovery after myelotoxic irradiation and that its absence accelerates AML and confers resistance to therapy in AML stem cells. It raises the possibility that targeting Lama4 signaling pathways may have therapeutic potential.
Structural insights into collagen binding by platelet receptor glycoprotein VI
Platelet glycoprotein VI (GPVI) is a potential target for antithrombotics. Feitsma and colleagues report the first crystal structure of GPVI complexed with collagen-related peptide and propose the structural basis of GPVI clustering on collagen fibers. This information will enhance design and screening for selective inhibitors that directly inhibit collagen binding to selectively inhibit activation of platelets.
Hemochromatosis classification: update and recommendations by the BIOIRON Society
Recent advances in the knowledge of the pathophysiology and molecular basis of iron metabolism highlight that hemochromatosis is caused by mutations in at least 5 genes. In this Special Report, experts from the BIOIRON Society propose an updated classification that is clinically applicable and incorporates the complexity of available state-of-the-art molecular testing. The report also provides a valuable overview of iron-loading conditions that must be distinguished from hemochromatosis.
