(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email firstname.lastname@example.org.
RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity, Cellot et al.
Histone methylation is a major regulator of gene expression and cell fate determination and has also been demonstrated to be dynamic and reversible. In this week’s issue of Blood, Cellot and colleagues utilized a shRNA functional screen to elucidate the role of the Jumonji domain-containing family of histone demethylating enzymes in hematopoietic stem cell (HSC) behavior. In the manuscript investigators identify Jarid1b as a negative regulator of HSC differentiation, observing that gene knockdown of Jarid1b increases the expression of genes such as the HOXA cluster associated with “stemness” while repressing differentiation genes, a process resulting in HSC expansion. Investigators also identified that Jhdm1f had an opposite effect on stem cells, as knockdown resulted in loss of bone marrow repopulating capacity. Although the orchestration of gene expression by histone methylases is incredibly complex, these studies begin to elucidate the role of histone methylation in cell fate determination and offer entry points for potential manipulation of the HSC differentiation program.
Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase domain, Soverini et al.
Soon after the initial success of tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) was reported, it was recognized that TKI resistance can develop as a result of mutations in the BCR-ABL kinase domain that affect how TKIs bind to the activation site. In this week’s issue of Blood, Soverini and colleagues report on the complexity of acquired BCR-ABL mutations in TKI-resistant CML as revealed by ultra-deep sequencing (UDS), reporting that the clonal architecture of resistant CML was far more complex than traditionally illustrated by conventional sequence analysis. This outcome suggests that current sequencing approaches utilized to predict TKI resistance may be inadequate and that patients who exhibit TKI resistance may be best served by UDS to determine the full range of BCR-ABL mutations that must be considered when choosing appropriate second- and third-line therapy.
Long-term remission of T-cell large granular lymphocyte leukemia associated with rheumatoid arthritis after rituximab therapy, Cornec et al.
T cell large granular lymphocyte leukemia (LGLL) can occur as a complication of rheumatoid arthritis (RA) and most commonly manifests as profound neutropenia. While the classification of LGLL and its associated neutropenia in the setting of RA as either a neoplastic disease or manifestation of underlying autoimmuune disease has been the source of much speculation, recent T-cell gene rearrangement studies have confirmed that the T cells are clonal and suggest that LGLL in the setting of RA is a neoplastic disease. However, in this issue of Blood, Cornec and colleagues report on two cases of RA-LGLL that, despite the continued presence of detectable clonal T-cell gene rearrangement, gained long-term control of RA symptoms and prolonged LGLL remission in response to rituximab. This suggests that at least some cases of RA-LGLL are driven by an underlying immune dysregulation and do not behave as T-cell malignancies despite the detection of clonal T cells.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
blood® is a registered trademark of the American Society of Hematology.
back to top